Essential Cell Biology 6th Edition

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PREFACE
The cell was first recognized as the fundamental unit of life in the nineteenth century, so by
now you might think that we should know everything there is to know about cells. Yet with each
new edition of Essential Cell Biology, its authors reexperience the joy of learning something new
and surprising. Indeed, working on a textbook is humbling—it reminds us that many of the most
fascinating questions in cell biology remain unanswered. How did cells first arise, and how have
billions of years of evolution allowed them to fill every possible ecological niche—from the hot
acid of volcanic springs to icy pools beneath the Antarctic surface? How do cells respond to
ever-changing environments, and how have their actions transformed our planet, paving the way
for our own eventual appearance? How is it possible for billions of cells to seamlessly cooperate
within complex multicellular organisms like ourselves?
Tackling such questions is among the many challenges that remain for the next generation of
cell biologists, some of whom may begin a wonderful, lifelong journey with this textbook. At the
same time, we hope that understanding cells—and the planet that, as living things, we all share—
will make us all better citizens and stewards of the global community. At the very least, we hope
that providing a window into how science approaches problems will help to reinforce trust in the
scientific process, rendering us all better equipped to make well-informed decisions about
increasingly sophisticated issues, from climate change and food security to biomedical
technologies and emerging epidemics.
In Essential Cell Biology we introduce readers to the fundamentals of cell biology. The Sixth
Edition has been updated to include many important new discoveries: we examine an unusual
archaeon, harvested from a steaming vent in the ocean floor, that appears to have struck up a
symbiotic relationship with a pair of other cells. This unanticipated partnership offers a
tantalizing glimpse of a process by which eukaryotic cells like our own may have evolved. We
provide new details about how our genetic information is packaged into chromosomes, and we
devote a great deal of effort—across several chapters—to discussing SARS-CoV-2, the virus
responsible for the COVID-19 pandemic. In addition to reviewing the virus’s structure and life
cycle, we describe the development of vaccines and drugs produced to fight it. Finally, as we do
for each new edition, we emphasize the powerful new techniques that allow us to study cells and
their components with unprecedented precision—including superresolution fluorescence
microscopy, cryo-electron microscopy, and the latest methods for DNA sequencing, protein
structure prediction, and gene editing. The whole illustration program has been extensively
reviewed and updated to include numerous new figures, micrographs, and movies.
Readers interested in learning how scientific inquisitiveness can fuel breakthroughs in our
understanding of cell biology will enjoy the stories of discovery presented in each chapter’s
“How We Know” feature. Packed with experimental data and design, these narratives illustrate
how biologists approach important questions and how experimental results shape future ideas.
As in previous editions, the questions in the margins and at the end of each chapter not only
test comprehension but also encourage careful thought and the application of newly acquired
information to a broader biological context. Some of these questions have more than one valid
answer and others invite speculation. Answers to all of the questions are included at the back of
the book, and many provide additional information or an alternative perspective on material
presented in the main text.

For those using the digital ebook, we have embedded thought-provoking “Check Your
Understanding” assessment questions at the end of each major chapter section. In addition,
Norton’s Smartwork platform offers a wealth of assignments at all levels of difficulty. Using
these questions, you can test your recall and understanding, as well as your ability to apply this
knowledge to evaluating experimental results and extracting information from figures, graphs,
and videos.
Nearly 200 video clips, animations, atomic structures, and high-resolution micrographs
complement the book and are available online. The movies are correlated with each chapter and
callouts are highlighted in color. This supplemental material, created to clarify complex and
critical concepts, highlights the intrinsic beauty of living cells. Also introduced in the ebook are a
new series of animated GIFs that we hope enhance your appreciation of many cellular and
molecular processes.
For those who wish to probe even more deeply, Molecular Biology of the Cell, now in its
Seventh Edition, offers a more detailed account of the life of the cell. The Smartwork
assessments associated with this edition, authored by John Wilson and Tim Hunt, provide a
treasure trove of challenging and provocative questions; we have drawn upon this tour-de-force
educational tool for some of the questions in Essential Cell Biology, and we are very grateful to
its authors.
Every chapter of Essential Cell Biology is the product of a communal effort: text, figures,
and even the dozens of new animated figure GIFs that appear throughout the ebook were revised
and refined as drafts circulated from one author to another—many times over and back again!
The numerous other individuals who have helped bring this project to fruition are credited in the
Acknowledgments that follow. Despite our best efforts, it is inevitable that errors will have crept
into the book, and we encourage eagle-eyed readers who find mistakes to let us know, so that we
can correct them in the next printing.
About the Cover
Natalie Orme created the art for the cover, using a technique called paper quilling. Quilling
was developed in early medieval Europe by nuns who made elaborate decorations using torn
strips of paper from the gilded edges of books. These were curled around a feather (quill) and
glued in patterns to ornament frames and book covers. The skill became a fashionable pursuit in
the eighteenth and nineteenth centuries and is once again seeing a resurgence of interest among
artists and craftspeople.
The front cover design makes use of various icons and motifs from the illustrations in the
book. On the back cover, in place of our usual author image, we have incorporated into the
design a variety of molecules and organisms, each of which has particular importance for one or
other of the authors. They include a cyclin-dependent kinase, a T4 bacteriophage, a zinnia, a
frog, a rat, a yeast, and a unicorn.
Acknowledgments
The authors acknowledge the many valuable contributions of professors and students from
around the world in the creation of this Sixth Edition. In particular, we received detailed reviews
from the following instructors, and we would like to thank them for their feedback, which allows

us to continue to improve this book:
Douglas Briant, University of Victoria
Marion Brodhagen, Western Washington University
Ron Dubreuil, University of Illinois at Chicago
Lisa Farmer, University of Houston
Valerie Haywood, Case Western Reserve University
Paul Himes, University of Louisville
Julie Hollien, The University of Utah
Todd Kostman, University of Wisconsin, Oshkosh
Michael Misamore, Texas Christian University
Edmund Rucker, University of Kentucky
Shannon Stevenson, University of Minnesota Duluth
Richard Walker, Virginia Tech
Robin Young, The University of British Columbia, Okanagan Campus
Amanda Zeigler, University of South Carolina, Columbia
We would also like to thank those reviewers whose comments helped inform the Fifth
Edition of this text, and whose contributions continue to be felt in this Sixth Edition:
Delbert Abi Abdallah, Thiel College, Pennsylvania
Ann Aguanno, Marymount Manhattan College
David W. Barnes, Georgia Gwinnett College
Manfred Beilharz, The University of Western Australia
Christopher Brandl, Western University, Ontario
David Casso, San Francisco State University
Shazia S. Chaudhry, The University of Manchester, United Kingdom
Heidi Engelhardt, University of Waterloo, Canada
Sarah Ennis, University of Southampton, United Kingdom
David Featherstone, The University of Illinois at Chicago
Yen Kang France, Georgia College
Barbara Frank, Idaho State University
Daniel E. Frigo, University of Houston
Marcos García-Ojeda, University of California, Merced
David L. Gard, The University of Utah
Adam Gromley, Lincoln Memorial University, Tennessee
P. Elly Holthuizen, University Medical Center Utrecht, The Netherlands
Harold Hoops, The State University of New York, Geneseo
Bruce Jensen, University of Jamestown, North Dakota
Andor Kiss, Miami University, Ohio
Annette Koenders, Edith Cowan University, Australia
Arthur W. Lambert, Whitehead Institute for Biomedical Research
Denis Larochelle, Clark University, Massachusetts
David Leaf, Western Washington University
Esther Leise, The University of North Carolina at Greensboro
Bernhard Lieb, University of Mainz, Germany
Julie Lively, Louisiana State University
Caroline Mackintosh, University of Saint Mary, Kansas
John Mason, The University of Edinburgh, Scotland

Craig Milgrim, Grossmont College, California
Arkadeep Mitra, City College, Kolkata, India
Niels Erik Møllegaard, University of Copenhagen
Javier Naval, University of Zaragoza, Spain
Marianna Patrauchan, Oklahoma State University
George Risinger, Oklahoma City Community College
Laura Romberg, Oberlin College, Ohio
Sandra Schulze, Western Washington University
Isaac Skromne, University of Richmond, Virginia
Anna Slusarz, Stephens College, Missouri
Richard Smith, University of Tennessee Health Science Center
Alison Snape, King’s College London
Marla Tipping, Providence College, Rhode Island
Jim Tokuhisa, Virginia Polytechnic Institute and State University
Guillaume van Eys, Maastricht University, The Netherlands
Barbara Vertel, Rosalind Franklin University of Medicine and Science, Illinois
Jennifer Waby, University of Bradford, United Kingdom
Dianne Watters, Griffith University, Australia
Allison Wiedemeier, University of Louisiana at Monroe
Elizabeth Wurdak, Saint John’s University, Minnesota
Kwok-Ming Yao, The University of Hong Kong
Foong May Yeong, National University of Singapore
We are also grateful to those readers around the world who alerted us to errors in the
previous edition.
Working on this book has been a pleasure, in part due to the many people who contributed to
its creation. Nigel Orme again worked closely with author Keith Roberts to generate the entire
illustration program with skill and care. Nigel designed the cover art, also used in chapter
openers; Natalie Orme then created it, using the old art of paper quilling. We owe a special debt
to Denise Schanck, our editor since 1998, who oversaw much of the revision process from 2018
through to her retirement in late 2021. Denise coordinated the initial reviewing, worked closely
with the authors on their chapters, took great care of us at our writing retreats, and kept us
inspired, motivated, and on schedule.
For bringing this edition to print, we also thank editor Jake Schindel for his keen eye,
kindness, and organizational prowess. Media editor Todd Pearson orchestrated the wealth of
online materials, including all video clips and animations, aided by senior associate media editor
Jasmine Ribeaux, associate media editor Lindsey Heale, and media editorial assistant Mandy
Lin. Their coordination of electronic media development has resulted in an unmatched suite of
resources for cell biology students and instructors alike. These have greatly benefited from the
work of John Wilson and Tim Hunt, whose tireless efforts to make The Problems Book for the
Molecular Biology of the Cell challenging and engaging have provided both inspiration and
examples for the Essential Cell Biology Smartwork program.
Clare Lewis deserves thanks for her assistance as the book moved through production. We
are grateful for marketing manager Holly Plank’s abundant enthusiasm and advocacy for our
book. Megan Schindel, Ted Szczepanski, and Patricia Wong are owed thanks for navigating the
permissions for this edition. And Jane Searle’s able management of production, Laura
Dragonette’s incredible attention to detail, and their shared knack for troubleshooting made the

book you hold in your hands a reality.
Last but not least, we are grateful, yet again, to our colleagues and our families for their
unflagging tolerance and support. We give our thanks to everyone in this long list.

Resources for Instructors and
Students
“Why Trust Science?” Web Resource
The How We Know panels in each chapter explain how investigators design and conduct the
experiments that bring them closer to understanding how biological systems work. But how are
the results of hundreds of thousands of experiments combined by scientists to produce the
scientific consensus needed to write a textbook?
In the Sixth Edition, we introduce a new “Why Trust Science” feature that focuses on how
science—through the combined efforts of a large community of scientists—is able to produce a
reliable body of knowledge that enormously benefits humanity. We include callouts for this
feature throughout the book, when we feel it’s most appropriate. Access it at any time at
digital.wwnorton.com/ecb6.
Glossary Terms
Throughout the book, boldface type has been used to highlight key terms at the point in a
chapter where the main discussion occurs. Italic type is used to set off important terms with a
lesser degree of emphasis. At the end of the book is an expanded glossary, covering all the major
terms common to cell biology; it should be the first resort for a reader who encounters an
unfamiliar technical word.
INSTRUCTOR RESOURCES
wwnorton.com/instructors
Smartwork
Smartwork is an easy-to-use online assessment tool that helps students become better
problem solvers through a variety of interactive question types, book-specific hints, and
extensive answer-specific feedback. Revised and updated for the Sixth Edition to further
emphasize critical thinking skills, Smartwork for Essential Cell Biology now also contains
primary literature activities, making it easier for instructors to introduce the reading of journal
articles into their course. Get started quickly with our premade assignments with questions
authored by master teachers, or take advantage of Smartwork’s flexibility by customizing
questions and adding your own content. Integration with your campus learning management
system (LMS) saves you time by allowing Smartwork grades to report directly to your LMS
gradebook, while individual and class-wide performance reports help you see students’ progress,
identify challenging concepts, and intervene with students who struggled with those concepts.
To access Smartwork, visit digital.wwnorton.com/ecb6.

Norton Teaching Tools
The Norton Teaching Tools site is your first stop when looking for creative, diverse
resources to refresh your syllabus or design a new one. Experienced instructors create resources
that are aligned with chapter topics, organized by activity type, and tagged to a common set of
learning objectives, making them easy to find and include in a flexible learning pathway based
on your course needs. The guide also features tips and best practices for assigning Norton’s
digital learning tools and addressing the most common course challenges. Example content
includes active-learning activities, primary literature activities, lecture PowerPoints, videos and
animations with descriptions, and questions for discussion based on the How We Know features
in the text.
Coursepacks
Easily add high-quality Norton digital resources to your online, hybrid, or lecture courses
through integrated links. Get started building your course with our easy-to-use integrated
resources; all activities can be accessed from within your existing learning management system.
Build your course using a carefully designed learning pathway, or customize your setup to best
reflect your teaching needs. Graded activities can be configured to report to the LMS course
grade book.
Test Bank
Norton Testmaker brings Norton’s high-quality testing materials online. Create assessments
for your course from anywhere with an Internet connection, without downloading files or
installing specialized software. Search and filter test bank questions by chapter, type, difficulty,
learning objectives, and other criteria. The test bank is written by Linda Huang, University of
Massachusetts Boston, and Cheryl D. Vaughan, Harvard Division of Continuing Education, and
revised by Eric Rutledge, Rensselaer Polytechnic Institute, Azad Gucwa, Farmingdale State
College, and Cayle Lisenbee, Arizona State College, and you can choose from over 1500
questions. Questions are available in multiple choice, multiple select, matching, and short answer
formats, with many using art from the textbook. Easily export your tests to Microsoft Word or
Common Cartridge files for your LMS.
To access Testmaker, visit wwnorton.com/instructors.
Animations and Videos
Essential Cell Biology is accompanied by over 150 movies that bring important concepts to
life. The clips have been thoroughly updated and expanded and are integrated throughout the text
and resources package, with links in the Norton Illumine Ebook and as embedded elements in
Smartwork questions. They can also be downloaded from the Norton Teaching Tools site, where
they are tagged to learning objectives and accompanied by suggestions for classroom use and
discussion questions.
To access the videos and animations, visit digital.wwnorton.com/ecb6.
Figure-integrated Lecture Outlines

All of the figures are integrated in PowerPoint, along with the section and concept headings
from the text, to give instructors a head start in creating lectures for their course.
Image Files
Every figure and photograph in the book is available for download in PowerPoint and JPEG
formats from wwnorton.com/instructors.
STUDENT RESOURCES
digital.wwnorton.com/ecb6
Animations and Videos
Streaming links give access to more than 150 videos and animations, bringing the concepts
of cell biology to life. Animations can also be accessed via the ebook and in select Smartwork
questions. The movies are correlated with each chapter and callouts in the text are highlighted in
color.
Norton Illumine Ebook
Norton’s high-quality content shines brighter through engaging and motivational features that
illuminate core concepts for all students in a supportive, accessible, and low-stakes environment.
Check Your Understanding questions with rich feedback motivate students and build confidence
in their learning, and Dynamic Figures engage students and help them visualize biological
processes. The active reading experience also includes the ability to highlight, take notes, search,
read offline, and more. Instructors can promote student accountability by adding their own
content and notes and through easy-to-use assignment tools in their LMS.

ABOUT THE AUTHORS
BRUCE ALBERTS received his PhD from Harvard University and is a professor in the
Department of Biochemistry and Biophysics at the University of California, San Francisco. He
was the editor-in-chief of Science from 2008 to 2013 and served as president of the U.S. National
Academy of Sciences from 1993 to 2005.
REBECCA HEALD received her PhD from Harvard University and is a professor of
molecular and cell biology at the University of California, Berkeley. She also serves as the cochair
of that department.
KAREN HOPKIN received her PhD from the Albert Einstein College of Medicine and is a
science writer. Her work has appeared in various scientific publications, including Science,
Proceedings of the National Academy of Sciences, and The Scientist, and she is a regular
contributor to Scientific American’s daily podcast, “60-Second Science.”
ALEXANDER JOHNSON received his PhD from Harvard University and is a professor in
the Department of Microbiology and Immunology at the University of California, San Francisco.
DAVID MORGAN received his PhD from the University of California, San Francisco,
where he is a professor in the Department of Physiology and vice dean for research in the School
of Medicine.
KEITH ROBERTS received his PhD from the University of Cambridge and was deputy
director of the John Innes Centre. He is professor emeritus at the University of East Anglia.
PETER WALTER received his PhD from The Rockefeller University in New York and is a
professor emeritus in the Department of Biochemistry and Biophysics at the University of
California, San Francisco. He was an investigator of the Howard Hughes Medical Institute and is
now senior vice president and institute director at Altos Labs in Redwood City.

LIST OF CHAPTERS and SPECIAL
FEATURES
CHAPTER 1 Cells: The Fundamental Units of Life 1
PANEL 1–1 Microscopy 12
TABLE 1–1 Historical Landmarks in Determining Cell Structure 26
PANEL 1–2 Cell Architecture 27
How We Know: Examining Life’s Common Mechanisms 33
TABLE 1–2 Some Model Organisms and Their Genomes 38
CHAPTER 2 Chemical Components of Cells 43
TABLE 2–1 Length and Strength of Some Chemical Bonds 53
TABLE 2–2 The Chemical Composition of a Bacterial Cell 56
How We Know: The Discovery of Macromolecules 64
PANEL 2–1 Chemical Bonds and Groups 70
PANEL 2–2 The Chemical Properties of Water 72
PANEL 2–3 The Principal Types of Weak Noncovalent Bonds 74
PANEL 2–4 An Outline of Some of the Types of Sugars 76
PANEL 2–5 Fatty Acids and Other Lipids 78
PANEL 2–6 The 20 Amino Acids Found in Proteins 80
PANEL 2–7 A Survey of the Nucleotides 82
CHAPTER 3 Energy, Catalysis, and Biosynthesis 85
TABLE 3–1 Relationship Between the Standard Free-Energy Change, ΔG°, and
the Equilibrium Constant 99
PANEL 3–1 Free Energy and Catalysis 100
How We Know: “High-Energy” Phosphate Bonds Power Cell Processes 107
TABLE 3–2 Some Activated Carriers Widely Used in Metabolism 113
CHAPTER 4 Protein Structure and Function 121
PANEL 4–1 A Few Examples of Some General Protein Functions 122
PANEL 4–2 Making and Using Antibodies 144
TABLE 4–1 Some Common Classes of Enzymes 146
TABLE 4–2 Historical Landmarks in Our Understanding of Proteins 163
How We Know: Harnessing Enzyme Performance for Human Benefit 165
PANEL 4–3 Cell Breakage and Initial Fractionation of Cell Extracts 170
PANEL 4–4 Protein Separation by Chromatography 172
PANEL 4–5 Protein Separation by Electrophoresis 173
PANEL 4–6 Protein Structure Determination 174
CHAPTER 5 DNA and Chromosomes 179
How We Know: Genes Are Made of DNA 203
CHAPTER 6 DNA Replication and Repair 209
How We Know: The Nature of Replication 212
TABLE 6–1 Proteins Involved in DNA Replication 223
TABLE 6–2 Error Rates 228
CHAPTER 7 From DNA to Protein: How Cells Read the Genome 237

TABLE 7–1 Types of RNA Produced in Cells 242
TABLE 7–2 The Three RNA Polymerases in Eukaryotic Cells 245
How We Know: Cracking the Genetic Code 257
TABLE 7–3 Antibiotics That Inhibit Bacterial Protein or RNA Synthesis 267
TABLE 7–4 Biochemical Reactions That Can Be Catalyzed by Ribozymes 272
CHAPTER 8 Control of Gene Expression 277
How We Know: Gene Regulation—The Story of Eve290
CHAPTER 9 How Genes and Genomes Evolve 307
TABLE 9–1 Viruses That Cause Human Disease 328
TABLE 9–2 Some Vital Statistics for the Human Genome 333
How We Know: Counting Genes 336
CHAPTER 10 Analyzing the Structure and Function of Genes 345
How We Know: Sequencing the Human Genome 360
CHAPTER 11 Membrane Structure 381
TABLE 11–1 Some Examples of Plasma Membrane Proteins and Their Functions
391
How We Know: Measuring Membrane Flow 400
CHAPTER 12 Transport Across Cell Membranes 405
TABLE 12–1 A Comparison of Ion Concentrations Inside and Outside a Typical
Mammalian Cell 408
TABLE 12–2 Some Examples of Transmembrane Pumps 420
How We Know: Squid Reveal Secrets of Membrane Excitability 430
TABLE 12–3 Some Examples of Ion Channels 438
CHAPTER 13 How Cells Obtain Energy from Food 445
TABLE 13–1 Some Types of Enzymes Involved in Glycolysis 449
PANEL 13–1 Details of the 10 Steps of Glycolysis 456
PANEL 13–2 The Complete Citric Acid Cycle 460
How We Know: Unraveling the Citric Acid Cycle 463
CHAPTER 14 Energy Generation in Mitochondria and Chloroplasts 473
TABLE 14–1 Mitochondrial Functions 478
TABLE 14–2 Product Yields from Glucose Oxidation 487
PANEL 14–1 Redox Potentials 490
How We Know: How Chemiosmotic Coupling Drives ATP Synthesis 494
CHAPTER 15 Intracellular Compartments and Protein Transport 515
TABLE 15–1 The Main Functions of the Membrane-enclosed Organelles of a
Eukaryotic Cell 517
TABLE 15–2 The Relative Volumes and Numbers of the Major Membraneenclosed
Organelles in a Liver Cell (Hepatocyte) 518
TABLE 15–3 Some Typical Signal Sequences 522
TABLE 15–4 Some Types of Coated Vesicles 535
How We Know: Tracking Protein and Vesicle Transport 541
CHAPTER 16 Cell Signaling 553
TABLE 16–1 Some Examples of Signal Molecules 556
TABLE 16–2 Some Foreign Substances That Act on Cell-Surface Receptors 564
TABLE 16–3 Some Cell Responses Mediated by Cyclic AMP 570
TABLE 16–4 Some Cell Responses Mediated by Phospholipase C Activation 572

How We Know: Untangling Cell Signaling Pathways 584
CHAPTER 17 Cytoskeleton 595
TABLE 17–1 Drugs That Affect Microtubules 609
How We Know: Pursuing Microtubule-associated Motor Proteins 612
TABLE 17–2 Drugs That Affect Filaments 618
CHAPTER 18 The Cell Cycle 635
TABLE 18–1 Some Eukaryotic Cell-Cycle Durations 637
How We Know: Discovery of Cyclins and Cdks 641
TABLE 18–2 The Major Cyclins and Cdks of Vertebrates 643
PANEL 18–1 The Principal Stages of M Phase in an Animal Cell 656
CHAPTER 19 Sexual Reproduction and Genetics 677
PANEL 19–1 Some Essentials of Classical Genetics 702
How We Know: Using SNPs to Get a Handle on Human Disease 710
CHAPTER 20 Cell Communities: Tissues, Stem Cells, and Cancer 717
TABLE 20–1 A Variety of Factors Can Contribute to Genetic Instability 748
TABLE 20–2 Examples of Cancer-critical Genes 755
How We Know: Making Sense of the Genes That Are Critical for Cancer 757

UNDERSTANDING SCIENCE: 20 “HOW
WE KNOW” PANELS AND A “WHY
TRUST SCIENCE?” WEB RESOURCE
In the Second Edition of Essential Cell Biology, we introduced a feature we call How We
Know. In these panels, we explain how investigators design and conduct experiments that bring
them closer to understanding how biological systems work. This approach to learning via
experimentation ultimately provides the material we present throughout the rest of the book, and
it allows us to make statements like “genes are made of DNA” (How We Know, Chapter 5, pp.
203–205) and “macromolecules are built from subunits held together by covalent bonds” (How
We Know, Chapter 2, pp. 64–65).
But how does this information make it from the laboratory to the textbook—or to a report on
the nightly news? And what happens when the results of one experiment contradict those of
another? For example, some scientists examining red blood cell membranes suggested that their
structure consisted of a gossamer lipid monolayer; others thought it was a triple-decker lipid
sandwich encased by an outer crust of proteins on both sides. How, then, did scientists ultimately
find out that cell membranes are fluid, phospholipid bilayers in which proteins are embedded? Or
that DNA is a double helix with its nucleotide bases on the inside, rather than a triple helix with
its bases radiating outward? (The triple-helix model was proposed by a Nobel Prize–winning
chemist, no less!)
Our understanding of cells and molecules continues to evolve, because science is not about
what any individual or group “believes.” Instead, scientific assertions and assumptions always
stand ready to be tested and toppled whenever new approaches for probing the biology of living
systems come along and provide data proving that our previous notions were not quite correct.
In the Sixth Edition, we introduce a new “Why Trust Science” feature that focuses on how
science—through the combined efforts of a cooperative community of scientists—is able to
produce a reliable body of knowledge that enormously benefits humanity. We include callouts
for this feature throughout the book, wherever we feel it’s most appropriate. Access it at any time
at digital.wwnorton.com/ecb6.

CONTENTS
Preface v
About the Authors xii
CHAPTER 1
Cells: The Fundamental Units of Life 1
UNITY AND DIVERSITY OF CELLS 2
Cells Vary Enormously in Appearance and Function 2
Living Cells All Have a Similar Basic Chemistry 3
Living Cells Are Self-replicating Collections of Catalysts 4
All Living Cells Have Apparently Evolved from the Same Ancestral Cell 5
Genes Provide Instructions for the Form, Function, and Behavior of Cells and
Organisms 6
SEEING CELL STRUCTURE 6
The Invention of the Light Microscope Led to the Discovery of Cells 7
Light Microscopes Reveal Some of a Cell’s Components 8
The Fine Structure of a Cell Is Revealed by Electron Microscopy 10
THE TREE OF LIFE 11
The Tree of Life Has Three Major Divisions 14
Eukaryotes Comprise the Domain of Life Most Familiar to Us 14
Bacteria Comprise the Most Diverse Collection of Organisms on Earth 16
The World of Archaea Is the Most Mysterious of Life’s Domains 17
THE EUKARYOTIC CELL 18
The Nucleus Is the Information Store of the Cell 19
Mitochondria Generate Usable Energy from Food Molecules 20
Chloroplasts Capture Energy from Sunlight 21
Internal Membranes Create Intracellular Compartments with Different Functions
22
The Cytosol Is a Concentrated Aqueous Gel of Large and Small Molecules 24
The Cytoskeleton Is Responsible for Directed Cell Movements 24
The Cytosol Is Far from Static 26
Many Eukaryotes Live as Solitary Cells 28
STUDYING MODEL SYSTEMS 28
Molecular Biologists Have Focused on Escherichia coli28
Brewer’s Yeast Is a Simple Eukaryote 29
Biologists Have Chosen Arabidopsis as a Model Plant 30
Model Animals Include Worms, Flies, Fish, and Mice 31
Studies Can Also Be Conducted on Humans and Their Cells 32
Genetic Studies of the Coronavirus SARS-CoV-2 Led to the Development of
Vaccines in Record Time 35
Comparing Genome Sequences Reveals Life’s Common Heritage 37
Genomes Contain More Than Just Genes 39
ESSENTIAL CONCEPTS 39
QUESTIONS 41

CHAPTER 2
Chemical Components of Cells 43
CHEMICAL BONDS 44
Cells Are Made of Relatively Few Types of Atoms 44
The Outermost Electrons Determine How Atoms Interact 45
Covalent Bonds Form by the Sharing of Electrons 47
Some Covalent Bonds Involve More Than One Electron Pair 48
Electrons in Covalent Bonds Are Often Shared Unequally 49
Covalent Bonds Are Strong Enough to Survive the Conditions Inside Cells 50
Ionic Bonds Form by the Gain and Loss of Electrons 50
Hydrogen Bonds Are Important Noncovalent Bonds for Many Biological
Molecules 51
Four Types of Weak Interactions Help Bring Molecules Together in Cells 52
Some Polar Molecules Form Acids and Bases in Water 53
SMALL MOLECULES IN CELLS 54
A Cell Is Formed from Carbon Compounds 55
Cells Contain Four Major Families of Small Organic Molecules 55
Sugars Are Both Energy Sources and Subunits of Polysaccharides 56
Fatty Acid Chains Are Components of Cell Membranes 58
Amino Acids Are the Subunits of Proteins 60
Nucleotides Are the Subunits of DNA and RNA 61
MACROMOLECULES IN CELLS 63
Each Macromolecule Contains a Specific Sequence of Subunits 63
Noncovalent Bonds Specify the Precise Shape of a Macromolecule 66
Noncovalent Bonds Also Allow a Macromolecule to Bind Other Selected
Molecules 67
ESSENTIAL CONCEPTS 68
QUESTIONS 69
CHAPTER 3
Energy, Catalysis, and Biosynthesis 85
THE USE OF ENERGY BY CELLS 86
Biological Order Is Made Possible by the Release of Heat Energy from Cells 87
Cells Can Convert Energy from One Form to Another 88
Photosynthetic Organisms Use Sunlight to Synthesize Organic Molecules 89
Cells Obtain Energy by the Oxidation of Organic Molecules 90
Oxidation and Reduction Involve Electron Transfers 91
FREE ENERGY AND CATALYSIS 93
Chemical Reactions Proceed in the Direction That Causes a Loss of Free Energy
93
Enzymes Reduce the Energy Needed to Initiate Spontaneous Reactions 93
The Free-Energy Change for a Reaction Determines Whether It Can Occur
Spontaneously 95
ΔG Changes as a Reaction Proceeds Toward Equilibrium 96
The Standard Free-Energy Change, ΔG°, Makes It Possible to Compare the
Energetics of Different Reactions 97
The Equilibrium Constant Is Directly Proportional to ΔG° 98

In Complex Reactions, the Equilibrium Constant Includes the Concentrations of
All Reactants and Products 98
For Sequential Reactions, the Changes in Free Energy Are Additive 102
Enzyme-catalyzed Reactions Depend on Rapid Molecular Collisions 103
Noncovalent Interactions Allow Enzymes to Bind Specific Molecules 103
The Equilibrium Constant Reflects the Strength of Noncovalent Binding
Interactions 104
ACTIVATED CARRIERS AND BIOSYNTHESIS 104
The Formation of an Activated Carrier Is Coupled to an Energetically Favorable
Reaction 105
ATP Is the Most Widely Used Activated Carrier 106
Energy Stored in ATP Is Often Harnessed to Join Two Molecules Together 110
NADH and NADPH Are Both Activated Carriers of Electrons 111
NADPH and NADH Have Different Roles in Cells 112
Cells Make Use of Many Other Activated Carriers 112
The Synthesis of Biological Polymers Requires an Energy Input 114
ESSENTIAL CONCEPTS 117
QUESTIONS 118
CHAPTER 4
Protein Structure and Function 121
THE SHAPE AND STRUCTURE OF PROTEINS 123
The Shape of a Protein Is Specified by Its Amino Acid Sequence 123
Proteins Fold into a Conformation of Lowest Energy 126
Proteins Come in a Wide Variety of Complicated Shapes 127
Hydrogen Bonds Within the Polypeptide Backbone Produce a Helices and b Sheets
130
Helices Form Readily in Biological Structures 131
β Sheets Form Rigid Structures at the Core of Many Proteins 133
Misfolded Proteins Can Form Amyloid Structures That Cause Disease 133
Proteins Exhibit Several Levels of Organization 134
Proteins Also Contain Unstructured Regions 135
Few of the Many Possible Polypeptide Chains Will Be Useful 135
Proteins Can Be Classified into Families 136
Large Protein Molecules Often Contain More Than One Polypeptide Chain 137
Proteins Can Assemble into Filaments, Sheets, or Spheres 138
Some Types of Proteins Have Elongated Fibrous Shapes 139
Extracellular Proteins Are Often Stabilized by Covalent Cross-Linkages 140
HOW PROTEINS WORK 141
All Proteins Bind to Other Molecules 141
Antibodies Bind to Their Target Ligands with Extraordinary Specificity 143
Enzymes Chemically Transform the Ligands to Which They Bind 146
Enzymes Greatly Accelerate the Speed of Chemical Reactions 147
Lysozyme Illustrates How an Enzyme Works 148
Many Drugs Inhibit Enzymes 150
Some Proteins Require Tightly Bound Small Molecules to Function 150
HOW PROTEINS ARE CONTROLLED 151

The Catalytic Activities of Enzymes Are Often Regulated by Other Molecules 152
Allosteric Enzymes Have Two or More Binding Sites That Influence One Another
152
Phosphorylation Can Control Protein Activity by Causing a Conformational
Change 154
Covalent Modifications Also Control the Location and Interaction of Proteins 155
Regulatory GTP-binding Proteins Are Switched On and Off by the Gain and Loss
of a Phosphate Group 156
ATP Hydrolysis Allows Motor Proteins to Produce Directed Movements in Cells
157
Proteins Often Form Large Complexes That Function as Machines 158
Many Interacting Proteins Are Brought Together by Scaffolds 159
Macromolecular Interactions Can Produce Large Biochemical Subcompartments in
Cells 160
HOW PROTEINS ARE STUDIED 161
Proteins Can Be Purified from Cells or Tissues 161
Determining a Protein’s Structure Begins with Determining Its Amino Acid
Sequence 162
Experimental and Computational Methods Convert Amino Acid Sequences into
Protein Structures 164
The Relatedness of Proteins Aids the Prediction of Protein Structure and Function
167
Genetic Engineering Methods Permit the Large-Scale Production, Analysis, and
Design of Proteins 167
ESSENTIAL CONCEPTS 168
QUESTIONS 176
CHAPTER 5
DNA and Chromosomes 179
THE STRUCTURE OF DNA 180
A DNA Molecule Consists of Two Complementary Chains of Nucleotides 181
The Structure of DNA Provides a Mechanism for Heredity 182
THE STRUCTURE OF EUKARYOTIC CHROMOSOMES 184
Eukaryotic DNA Is Packaged into Multiple Chromosomes 185
Chromosomes Organize and Carry Genetic Information 186
Specialized DNA Sequences Are Required for DNA Replication and Chromosome
Segregation 187
Interphase Chromosomes Are Not Randomly Distributed Within the Nucleus 188
The DNA in Chromosomes Is Highly Condensed 189
Nucleosomes Are the Basic Units of Eukaryotic Chromosome Structure 190
Interphase Chromosomes Are Further Organized into Loops by Large Protein
Rings 193
Chromosomes Undergo an Additional Level of Packing at Mitosis 194
THE REGULATION OF CHROMOSOME STRUCTURE 195
Changes in Nucleosomes Allow Access to DNA 195
Interphase Chromosomes Contain Both Highly Condensed and More Extended
Forms of Chromatin 197

Heterochromatin Can Spread Along a Chromosome to Silence Nearby Genes 198
X-Inactivation Represents an Extreme Form of Gene Silencing 199
Heterochromatin Can Be Inherited by Subsequent Generations of Cells 200
ESSENTIAL CONCEPTS 201
QUESTIONS 206
CHAPTER 6
DNA Replication and Repair 209
DNA REPLICATION 210
Base-pairing Enables DNA Replication 210
DNA Synthesis Begins at Replication Origins 211
Two Replication Forks Form at Each Replication Origin 215
DNA Polymerase Synthesizes DNA Using a Parent Strand as a Template 215
The Replication Fork Is Asymmetrical 216
DNA Polymerase Is Self-Correcting 218
Short Lengths of RNA Act as Primers for DNA Synthesis 218
Proteins at a Replication Fork Cooperate to Form a Replication Machine 220
Telomerase Replicates the Ends of Eukaryotic Chromosomes 223
Telomere Length Varies by Cell Type and with Age 224
DNA REPAIR 225
DNA Damage Occurs Continually in Cells 225
Cells Possess a Variety of Mechanisms for Repairing DNA 227
A DNA Mismatch Repair System Removes Replication Errors That Escape
Proofreading 228
Double-Strand DNA Breaks Require a Different Strategy for Repair 229
Homologous Recombination Can Flawlessly Repair DNA Double-strand Breaks
230
Failure to Repair DNA Damage Can Have Severe Consequences for a Cell or
Organism 232
A Record of the Fidelity of DNA Replication and Repair Is Preserved in Genome
Sequences 233
ESSENTIAL CONCEPTS 234
QUESTIONS 235
CHAPTER 7
From DNA to Protein: How Cells Read the Genome 237
FROM DNA TO RNA 238
Portions of DNA Sequence Are Transcribed into RNA 239
Transcription Produces RNA That Is Complementary to One Strand of DNA 240
Cells Produce Various Types of RNA 242
Signals in the DNA Tell RNA Polymerase Where to Start and Stop Transcription
243
Initiation of Eukaryotic Gene Transcription Is a Complex Process 245
Eukaryotic RNA Polymerase Requires the Assistance of a Collection of Accessory
Proteins 245
Eukaryotic mRNAs Are Processed in the Nucleus 247
In Eukaryotes, Protein-coding Genes Are Interrupted by Noncoding Sequences
Called Introns 248

Introns Are Removed from Pre-mRNAs by RNA Splicing 249
RNA Synthesis and Processing Take Place in Membraneless Compartments Within
the Nucleus 252
Mature Eukaryotic mRNAs Are Exported from the Nucleus 253
mRNA Molecules Are Eventually Degraded in the Cytosol 254
FROM RNA TO PROTEIN 254
An mRNA Sequence Is Decoded in Sets of Three Nucleotides 255
tRNA Molecules Match Amino Acids to Codons in mRNA 256
Specific Enzymes Couple tRNAs to the Correct Amino Acid 260
The mRNA Message Is Decoded on Ribosomes 261
The Ribosome Is a Ribozyme 262
Specific Codons in an mRNA Signal the Ribosome Where to Start and to Stop
Protein Synthesis 264
Proteins Are Produced on Polyribosomes 266
Inhibitors of Prokaryotic Protein Synthesis Are Used as Antibiotics 267
Controlled Protein Breakdown Helps Regulate the Amount of Each Protein in a
Cell 268
There Are Many Steps Between DNA and Protein 269
RNA AND THE ORIGINS OF LIFE 269
Life Requires Autocatalysis 270
RNA Can Store Information and Catalyze Chemical Reactions 271
RNA Is Thought to Predate DNA in Evolution 272
ESSENTIAL CONCEPTS 273
QUESTIONS 275
CHAPTER 8
Control of Gene Expression 277
AN OVERVIEW OF GENE EXPRESSION 278
The Different Cell Types of a Multicellular Organism Contain the Same DNA
278
Different Cell Types Produce Different Sets of Proteins 280
A Cell Can Change the Expression of Its Genes in Response to External Signals
280
Gene Expression Can Be Regulated at Various Steps from DNA to RNA to Protein
280
HOW TRANSCRIPTION IS REGULATED 281
Transcription Regulators Bind to Regulatory DNA Sequences 281
Transcription Switches Allow Cells to Respond to Changes in Their Environment
283
Repressors Turn Genes Off and Activators Turn Them On 284
The Lac Operon Is Controlled by an Activator and a Repressor 285
Eukaryotic Transcription Regulators Control Gene Expression from a Distance 286
Eukaryotic Transcription Regulators Help Initiate Transcription by Recruiting
Chromatin-modifying Proteins 287
The Arrangement of Chromosomes into Looped Domains Keeps Enhancers in
Check 288
GENERATING SPECIALIZED CELL TYPES 288

Eukaryotic Genes Are Controlled by Combinations of Transcription Regulators
289
The Expression of Different Genes Can Be Coordinated by a Single Protein 292
Combinatorial Control Is Used to Generate Different Cell Types 293
The Formation of an Entire Organ Can Be Triggered by a Single Transcription
Regulator 294
Transcription Regulators Can Be Used to Experimentally Direct the Formation of
Specific Cell Types in Culture 295
Differentiated Cells Maintain Their Identity 296
POST-TRANSCRIPTIONAL CONTROLS 298
mRNAs Contain Sequences That Control Their Translation 298
Regulatory RNAs Control the Expression of Thousands of Genes 299
MicroRNAs Direct the Destruction of Target mRNAs 299
Small Interfering RNAs Protect Cells from Infections 299
Bacteria Use Small Noncoding RNAs to Protect Themselves from Viruses 301
Thousands of Long Noncoding RNAs May Also Regulate Mammalian Gene
Activity 302
ESSENTIAL CONCEPTS 303
QUESTIONS 304
CHAPTER 9
How Genes and Genomes Evolve 307
GENERATING GENETIC VARIATION 308
In Sexually Reproducing Organisms, Only Changes to the Germ Line Are Passed
On to Progeny 309
Point Mutations Are Caused by Failures of the Normal Mechanisms for Copying
and Repairing DNA 311
Mutations Can Also Change the Regulation of a Gene 312
DNA Duplications Give Rise to Families of Related Genes 312
Duplication and Divergence Produced the Globin Gene Family 314
Whole-Genome Duplications Have Shaped the Evolutionary History of Many
Species 315
Novel Genes Can Be Created by Exon Shuffling 316
The Evolution of Genomes Has Been Profoundly Influenced by Mobile Genetic
Elements 317
Genes Can Be Exchanged Between Organisms by Horizontal Gene Transfer 318
RECONSTRUCTING LIFE’S FAMILY TREE 318
Genetic Changes That Provide a Selective Advantage Are Likely to Be Preserved
319
Closely Related Organisms Have Genomes That Are Similar in Organization as
Well as Sequence 320
Functionally Important Genome Regions Show Up as Islands of Conserved DNA
Sequence 320
Genome Comparisons Show That Vertebrate Genomes Gain and Lose DNA
Rapidly 322
Sequence Conservation Allows Us to Trace Even the Most Distant Evolutionary
Relationships 323

MOBILE GENETIC ELEMENTS AND VIRUSES 324
Mobile Genetic Elements Encode the Components They Need for Movement 325
The Human Genome Contains Two Major Families of Transposable Sequences
326
Viruses Can Move Between Cells and Organisms 327
Coronaviruses Such as SARS-CoV-2 Use a Special Replicase to Copy Their RNA
Genomes 329
Retroviruses Reverse the Normal Flow of Genetic Information 329
EXAMINING THE HUMAN GENOME 331
The Nucleotide Sequences of Human Genomes Show How Our Genes Are
Arranged 332
Differences in Gene Regulation Help Explain How Animals with Similar Genomes
Can Be So Different 335
The Genome of Extinct Neanderthals Reveals Much About What Makes Us
Human 338
Genome Variation Contributes to Our Individuality—But How? 338
ESSENTIAL CONCEPTS 340
QUESTIONS 341
CHAPTER 10
Analyzing the Structure and Function of Genes 345
ISOLATING AND CLONING DNA MOLECULES 346
Restriction Enzymes Cut DNA Molecules at Specific Sites 347
Gel Electrophoresis Separates DNA Fragments of Different Sizes 347
DNA Cloning Begins with the Production of Recombinant DNA 349
Recombinant DNA Can Be Copied Inside Bacterial Cells 349
An Entire Genome Can Be Represented in a DNA Library 351
Hybridization Provides a Sensitive Way to Detect Specific Nucleotide Sequences
352
PCR Can Be Used to Produce Specific DNA Fragments in a Test Tube 353
PCR Can Be Used for Diagnostic and Forensic Applications 354
SEQUENCING DNA 355
Dideoxy Sequencing Depends on the Analysis of DNA Chains Terminated at
Every Position 358
Next-Generation Sequencing Techniques Make Genome Sequencing Faster and
Cheaper 358
Comparative Genome Analyses Can Identify Genes and Predict Their Function 362
EXPLORING GENE FUNCTION 362
Analysis of mRNAs Provides a Snapshot of Gene Expression 363
In Situ Hybridization Reveals When and Where a Gene Is Expressed 364
Ribosome Profiling Reveals Which mRNAs in a Cell Are Being Translated into
Proteins 365
Reporter Genes Allow Specific Proteins to Be Tracked in Living Cells 365
The Study of Mutants Can Help Reveal the Function of a Gene 367
RNA Interference (RNAi) Inhibits the Activity of Specific Genes 368
A Known Gene Can Be Deleted or Replaced with an Altered Version 369
Genes Can Be Edited with Great Precision Using the Bacterial CRISPR System

371
Mutant Organisms Provide Useful Models of Human Disease 373
Transgenic Plants Are Important for Both Cell Biology and Agriculture 373
DNA Cloning Allows Any Protein to Be Produced in Large Amounts 375
ESSENTIAL CONCEPTS 376
QUESTIONS 377
CHAPTER 11
Membrane Structure 381
THE LIPID BILAYER 382
Membrane Lipids Form Bilayers in Water 383
The Lipid Bilayer Is a Flexible Two-dimensional Fluid 386
The Fluidity of a Lipid Bilayer Depends on Its Composition 387
Membrane Assembly Begins in the Endoplasmic Reticulum 389
Certain Phospholipids Are Confined to One Side of the Membrane 389
MEMBRANE PROTEINS 391
Membrane Proteins Associate with the Lipid Bilayer in Different Ways 392
A Polypeptide Chain Usually Crosses the Lipid Bilayer as an a Helix 393
Membrane Proteins Can Be Solubilized in Detergents 394
We Know the Complete Structure of Relatively Few Membrane Proteins 395
The Plasma Membrane Is Reinforced by the Underlying Cell Cortex 396
A Cell Can Restrict the Movement of Its Membrane Proteins 397
The Cell Surface Is Coated with Carbohydrate 398
ESSENTIAL CONCEPTS 402
QUESTIONS 403
CHAPTER 12
Transport Across Cell Membranes 405
PRINCIPLES OF TRANSMEMBRANE TRANSPORT 406
Lipid Bilayers Are Impermeable to Ions and Most Uncharged Polar Molecules
406
Membrane Transport Proteins Facilitate the Movement of Select Substances
Across Cell Membranes 407
The Ion Concentrations Inside a Cell Are Very Different from Those Outside 407
Differences in the Concentration of Inorganic Ions Across a Cell Membrane Create
a Membrane Potential 408
Solutes Cross Membranes by Either Passive or Active Transport 409
Both the Concentration Gradient and Membrane Potential Influence the Passive
Transport of Charged Solutes 409
Water Moves Across Cell Membranes Down Its Concentration Gradient—a
Process Called Osmosis 410
TRANSPORTERS AND THEIR FUNCTIONS 412
Passive Transporters Move a Solute Along Its Electrochemical Gradient 412
Pumps Actively Transport a Solute Against Its Electrochemical Gradient 413
The Na + Pump in Animal Cells Uses Energy Supplied by ATP to Expel Na + and
Bring in K + 414
The Na + Pump Generates a Steep Concentration Gradient of Na + Across the
Plasma Membrane 415

Ca 2+ Pumps Keep the Cytosolic Ca 2+ Concentration Low 416
Gradient-driven Pumps Exploit Solute Gradients to Mediate Active Transport 416
The Electrochemical Na + Gradient Drives the Transport of Glucose Across the
Plasma Membrane of Animal Cells 417
Electrochemical H + Gradients Drive the Transport of Solutes in Plants, Fungi, and
Bacteria 419
ION CHANNELS AND THE MEMBRANE POTENTIAL 419
Ion Channels Are Ion-selective and Gated 420
Membrane Potential Is Governed by the Permeability of a Membrane to Specific
Ions 422
Ion Channels Randomly Snap Between Open and Closed States 424
Different Types of Stimuli Influence the Opening and Closing of Ion Channels 425
Voltage-gated Ion Channels Respond to the Membrane Potential 427
ION CHANNELS AND NERVE CELL SIGNALING 428
Action Potentials Allow Rapid Long-Distance Communication Along Axons 428
Action Potentials Are Mediated by Voltage-gated Cation Channels 429
Voltage-gated Ca 2+ Channels in Nerve Terminals Convert an Electrical Signal into
a Chemical Signal 434
Transmitter-gated Ion Channels in the Postsynaptic Membrane Convert the
Chemical Signal Back into an Electrical Signal 435
Neurotransmitters Can Be Excitatory or Inhibitory 436
Most Psychoactive Drugs Alter the Activity of Neurotransmitter Receptors 437
The Complexity of Synaptic Signaling Enables Us to Think, Act, Learn, and
Remember 438
Light-gated Ion Channels Can Be Used to Transiently Activate or Inactivate
Neurons in Living Animals 439
ESSENTIAL CONCEPTS 441
QUESTIONS 442
CHAPTER 13
How Cells Obtain Energy from Food 445
THE BREAKDOWN AND UTILIZATION OF SUGARS AND FATS 446
Food Molecules Are Broken Down in Three Stages 446
Glycolysis Extracts Energy from the Splitting of Sugar 448
Glycolysis Produces Both ATP and NADH 449
Fermentations Can Produce ATP in the Absence of Oxygen 451
Glycolytic Enzymes Couple Oxidation to Energy Storage in Activated Carriers 452
Several Types of Organic Molecules Are Converted to Acetyl CoA in the
Mitochondrial Matrix 453
The Citric Acid Cycle Generates NADH by Oxidizing Acetyl Groups to CO 2 458
Many Biosynthetic Pathways Begin with Glycolysis or the Citric Acid Cycle 459
Electron Transport Drives the Synthesis of the Majority of the ATP in Most Cells
462
REGULATION OF METABOLISM 465
Catabolic and Anabolic Reactions Are Organized and Regulated 466
Feedback Regulation Allows Cells to Switch from Glucose Breakdown to Glucose
Synthesis 466

Cells Store Food Molecules in Special Reservoirs to Prepare for Periods of Need
467
ESSENTIAL CONCEPTS 470
QUESTIONS 471
CHAPTER 14
Energy Generation in Mitochondria and Chloroplasts 473
Cells Obtain Most of Their Energy by a Membrane-based Mechanism 474
Chemiosmotic Coupling Is an Ancient Process, Preserved in Present-Day Cells
475
MITOCHONDRIA AND OXIDATIVE PHOSPHORYLATION 476
Mitochondria Are Dynamic in Shape, Location, Number, and Function 477
A Mitochondrion Contains an Outer Membrane, an Inner Membrane, and Two
Internal Compartments 479
The Citric Acid Cycle Generates High-Energy Electrons Required for ATP
Production 480
The Movement of Electrons Is Coupled to the Pumping of Protons 481
Electrons Pass Through Three Large Enzyme Complexes in the Inner
Mitochondrial Membrane 482
Proton Pumping Produces a Steep Electrochemical Proton Gradient Across the
Inner Mitochondrial Membrane 483
ATP Synthase Uses the Energy Stored in the Electrochemical Proton Gradient to
Produce ATP 484
The Electrochemical Proton Gradient Also Drives Transport Across the Inner
Mitochondrial Membrane 485
The Rapid Conversion of ADP to ATP in Mitochondria Maintains a High
ATP/ADP Ratio in Cells 486
Cell Respiration Is Amazingly Efficient 487
MOLECULAR MECHANISMS OF ELECTRON TRANSPORT AND
PROTON PUMPING 488
Protons Are Readily Moved by the Transfer of Electrons 488
The Redox Potential Is a Measure of Electron Affinities 489
Electron Transfers Release Large Amounts of Energy 489
Metals Tightly Bound to Proteins Form Versatile Electron Carriers 491
Cytochrome c Oxidase Catalyzes the Reduction of Molecular Oxygen 493
CHLOROPLASTS AND PHOTOSYNTHESIS 496
Chloroplasts Resemble Mitochondria but Have an Extra Compartment—the
Thylakoid 497
Photosynthesis Generates—and Then Consumes—ATP and NADPH 498
Chlorophyll Molecules Absorb the Energy of Sunlight 499
Excited Chlorophyll Molecules Funnel Energy into a Reaction Center 499
A Pair of Photosystems Cooperate to Generate Both ATP and NADPH 500
Oxygen Is Generated by a Water-splitting Complex Associated with Photosystem
II 501
The Special Pair in Photosystem I Receives Its Electrons from Photosystem II 502
Carbon Fixation Uses ATP and NADPH to Convert CO 2 into Sugars 503
Sugars Generated by Carbon Fixation Can Either Be Stored as Starch or Used to

Produce ATP and Other Organic Molecules 506
THE EVOLUTION OF ENERGY-GENERATING SYSTEMS 507
Oxidative Phosphorylation Evolved in Stages 507
Photosynthetic Bacteria Made Even Fewer Demands on Their Environment 508
The Lifestyle of Methanococcus Suggests That Chemiosmotic Coupling Is an
Ancient Process 510
ESSENTIAL CONCEPTS 511
QUESTIONS 512
CHAPTER 15
Intracellular Compartments and Protein Transport 515
MEMBRANE-ENCLOSED ORGANELLES 516
Eukaryotic Cells Contain a Basic Set of Membrane-enclosed Organelles 516
Membrane-enclosed Organelles Arose as Cells Grew Larger 519
PROTEIN SORTING 520
Proteins Are Transported into Organelles by Three Mechanisms 520
Signal Sequences Direct Proteins to the Correct Compartment 522
Proteins Enter the Nucleus Through Nuclear Pores 523
Proteins Unfold to Enter Mitochondria and Chloroplasts 525
Proteins Enter Peroxisomes from Both the Cytosol and the Endoplasmic Reticulum
526
Proteins Enter the Endoplasmic Reticulum While Being Synthesized 526
Soluble Proteins Made on the ER Are Released into the ER Lumen 528
Additional Hydrophobic Signal Sequences Determine the Arrangement of a
Transmembrane Protein in the Lipid Bilayer 529
Junctions Between the ER and Other Organelles Facilitate the Transfer of Specific
Lipids 530
VESICULAR TRANSPORT 532
Transport Vesicles Carry Soluble Proteins and Membrane Between Compartments
532
Vesicle Budding Is Driven by the Assembly of a Protein Coat 533
Vesicle Docking Depends on Tethers and SNAREs 535
SECRETORY PATHWAYS 536
Most Proteins Are Covalently Modified in the ER 536
Exit from the ER Is Controlled to Ensure Protein Quality 538
The Size of the ER Is Controlled by the Demand for Protein Folding 538
Proteins Are Further Modified and Sorted in the Golgi Apparatus 539
Secretory Proteins Are Released from the Cell by Exocytosis 540
ENDOCYTIC PATHWAYS 544
Specialized Phagocytic Cells Ingest Large Particles 544
Fluid and Macromolecules Are Taken Up by Pinocytosis 545
Receptor-mediated Endocytosis Provides a Specific Route into Animal Cells 545
Endocytosed Macromolecules Are Sorted in Endosomes 547
Lysosomes Are the Principal Sites of Intracellular Digestion 548
ESSENTIAL CONCEPTS 549
QUESTIONS 551
CHAPTER 16

Cell Signaling 553
GENERAL PRINCIPLES OF CELL SIGNALING 554
Signals Can Act over a Long or Short Range 554
Extracellular Signals Act Through Specific Receptors to Change Cell Behaviors
557
A Cell’s Response to a Signal Can Be Fast or Slow 558
Cell-Surface Receptors Relay Extracellular Signals via Intracellular Signaling
Pathways 559
Some Intracellular Signaling Proteins Act as Molecular Switches 561
Cell-Surface Receptors Fall into Three Main Classes 563
Ion-Channel-coupled Receptors Convert Chemical Signals into Electrical Ones 564
G-PROTEIN-COUPLED RECEPTORS 565
Stimulation of GPCRs Activates G-Protein Subunits 565
Some Bacterial Toxins Cause Disease by Altering the Activity of G Proteins 567
Some G Proteins Directly Regulate Ion Channels 568
Many G Proteins Activate Membrane-bound Enzymes That Produce Small
Messenger Molecules 569
The Cyclic AMP Signaling Pathway Can Activate Enzymes and Turn On Genes
569
The Inositol Phospholipid Pathway Triggers a Rise in Intracellular Ca 2+ 572
A Ca 2+ Signal Triggers Many Biological Processes 573
Some GPCR Signaling Pathways Generate a Dissolved Gas That Carries a Signal
to Adjacent Cells 574
GPCR-triggered Intracellular Signaling Pathways Can Achieve Astonishing Speed,
Sensitivity, and Adaptability 575
ENZYME-COUPLED RECEPTORS 577
Activated RTKs Recruit a Complex of Intracellular Signaling Proteins 578
Most RTKs Activate the Monomeric GTPase Ras 580
RTKs Activate Phosphoinositide 3-Kinase to Produce Lipid Docking Sites in the
Plasma Membrane 581
Some Receptors Activate a Fast Track to the Nucleus 583
Some Extracellular Signal Molecules Cross the Plasma Membrane and Bind to
Intracellular Receptors 586
Plants Make Use of Receptors and Signaling Strategies That Differ from Those
Used by Animals 588
Protein Kinase Networks Integrate Information to Control Complex Cell Behaviors
588
ESSENTIAL CONCEPTS 590
QUESTIONS 592
CHAPTER 17
Cytoskeleton 595
INTERMEDIATE FILAMENTS 597
Intermediate Filaments Are Strong and Ropelike 597
Intermediate Filaments Strengthen Cells Against Mechanical Stress 599
The Nuclear Envelope Is Supported by a Meshwork of Intermediate Filaments 600
Linker Proteins Connect Cytoskeletal Filaments and Bridge the Nuclear Envelope

601
MICROTUBULES 602
Microtubules Are Hollow Tubes with Structurally Distinct Ends 603
Microtubules Grow from Specialized Microtubule-organizing Centers 603
Microtubules Display Dynamic Instability 605
Microtubules Organize the Cell Interior 606
Microtubule-binding Proteins Regulate Microtubule Dynamics and Organization
607
Microtubule-associated Motor Proteins Drive Intracellular Transport 609
Microtubules and Motor Proteins Position Organelles in the Cytoplasm 610
Cilia and Flagella Contain Stable Microtubules Moved by Dynein 611
ACTIN FILAMENTS 616
Actin Filaments Are Thin and Flexible 616
Actin and Tubulin Polymerize by Similar Mechanisms 617
Many Proteins Bind to Actin and Modify Its Properties 618
Myosins Are Actin-binding Motor Proteins 619
A Cortex Rich in Actin Filaments Underlies the Plasma Membrane of Most
Eukaryotic Cells 620
Cell Crawling Depends on Cortical Actin 620
Actin-binding Proteins Influence the Type of Protrusions Formed at the Leading
Edge 622
Extracellular Signals Can Alter the Arrangement of Actin Filaments 623
Actin Filaments Work with Microtubules to Establish Cell Polarity 624
MUSCLE CONTRACTION 625
Muscle Contraction Depends on Interacting Filaments of Actin and Myosin 625
Actin Filaments Slide Against Myosin Filaments During Muscle Contraction 626
Muscle Contraction Is Triggered by a Sudden Rise in Cytosolic Ca 2+ 628
Different Types of Muscle Cells Perform Different Functions 630
ESSENTIAL CONCEPTS 631
QUESTIONS 632
CHAPTER 18
The Cell Cycle 635
OVERVIEW OF THE CELL CYCLE 636
The Eukaryotic Cell Cycle Usually Includes Four Phases 637
The Cell-Cycle Control System Triggers the Major Processes of the Cell Cycle
638
Cell-Cycle Control Is Similar in All Eukaryotes 639
THE CELL-CYCLE CONTROL SYSTEM 639
The Cell-Cycle Control System Depends on Cyclically Activated Protein Kinases
Called Cdks 639
Different Cyclin–Cdk Complexes Trigger Different Steps in the Cell Cycle 640
Cyclin Concentrations Are Regulated by Transcription and by Proteolysis 643
The Activity of Cyclin–Cdk Complexes Is Controlled by Phosphorylation,
Dephosphorylation, and Cdk Inhibitor Proteins 644
Protein Phosphatases Reverse the Effects of Cdks 644
Hundreds of Cdk Target Proteins Are Phosphorylated in a Defined Order 645

The Cell-Cycle Control System Can Pause the Cycle in Various Ways 646
G 1 PHASE 646
Cdks Are Stably Inactivated in Early G 1 647
Mitogens Promote Production of Cyclins That Stimulate Cell Division 647
DNA Damage Can Temporarily Halt Progression Through G 1 648
Cells Can Delay Division for Prolonged Periods by Entering Specialized
Nondividing States 649
S PHASE 650
S-Cdk Initiates DNA Replication and Blocks Re-Replication 650
Incomplete Replication Can Arrest the Cell Cycle in G 2 650
M PHASE 651
M-Cdk Drives Entry into Mitosis 652
Cohesins and Condensins Help Configure Duplicated Chromosomes for
Segregation 652
Different Cytoskeletal Assemblies Carry Out Mitosis and Cytokinesis 653
M Phase Occurs in Stages 654
MITOSIS 654
Centrosomes Duplicate to Help Form the Two Poles of the Mitotic Spindle 654
The Mitotic Spindle Is a Dynamic Microtubule-based Machine 655
Chromosomes Attach to the Mitotic Spindle at Prometaphase 658
Chromosomes Assist in the Assembly of the Mitotic Spindle 659
Chromosomes Line Up at the Spindle Equator at Metaphase 659
Proteolysis Triggers Sister-Chromatid Separation at Anaphase 660
Chromosomes Segregate During Anaphase 660
An Unattached Chromosome Will Prevent Sister-Chromatid Separation 661
The Nuclear Envelope Re-forms at Telophase 661
CYTOKINESIS 662
The Mitotic Spindle Determines the Plane of Cleavage 662
The Contractile Ring of Animal Cells Is Made of Actin and Myosin Filaments 664
Cytokinesis in Plant Cells Involves the Formation of a New Cell Wall 664
Membrane-enclosed Organelles Must Be Distributed to Daughter Cells When a
Cell Divides 666
CONTROL OF CELL GROWTH, CELL DIVISION, AND CELL
SURVIVAL 666
Animal Cells Require Extracellular Signals to Survive, Grow, and Divide 666
Mitogens Stimulate Cell Division by Promoting Entry into the Cell Cycle 667
Growth Factors Promote an Increase in Cell Size 667
Apoptosis Helps Regulate Animal Cell Numbers 668
Apoptosis Is Mediated by an Intracellular Proteolytic Cascade 669
The Intrinsic Apoptotic Death Program Is Regulated by the Bcl2 Family of
Intracellular Proteins 670
Signals from Other Cells Activate the Extrinsic Apoptotic Death Program 671
Survival Factors Promote Cell Survival by Suppressing Apoptosis 671
Some Extracellular Signal Proteins Inhibit Cell Survival, Division, or Growth 672
ESSENTIAL CONCEPTS 673
QUESTIONS 675

CHAPTER 19
Sexual Reproduction and Genetics 677
THE BENEFITS OF SEX 678
Sexual Reproduction Involves Both Diploid and Haploid Cells 678
Sexual Reproduction Generates Genetic Diversity 679
Sexual Reproduction Gives Organisms a Competitive Advantage in a Changing
Environment 679
MEIOSIS AND FERTILIZATION 680
Meiosis Involves One Round of DNA Replication Followed by Two Rounds of
Nuclear Division 681
Duplicated Homologous Chromosomes Pair During Meiotic Prophase 681
Crossing-Over Occurs Between the Duplicated Maternal and Paternal
Chromosomes in Each Bivalent 683
Chromosome Pairing and Crossing-Over Ensure the Proper Segregation of
Homologs 685
The Second Meiotic Division Produces Haploid Daughter Nuclei 686
Haploid Gametes Contain Reassorted Genetic Information 687
Meiosis Is Not Flawless 688
Fertilization Reconstitutes a Complete Diploid Genome 689
MENDEL AND THE LAWS OF INHERITANCE 689
Mendel Studied Traits That Are Inherited in a Discrete Fashion 690
Mendel Disproved the Alternative Theories of Inheritance 690
Mendel’s Experiments Revealed the Existence of Dominant and Recessive Alleles
691
Each Gamete Carries a Single Allele for Each Character 692
Mendel’s Law of Segregation Applies to All Sexually Reproducing Organisms 693
Alleles for Different Traits Segregate Independently 695
The Behavior of Chromosomes During Meiosis Underlies Mendel’s Laws of
Inheritance 695
Genes That Lie on the Same Chromosome Can Segregate Independently by
Crossing-Over 696
Mutations in Genes Can Cause a Loss of Function or a Gain of Function 698
Each of Us Carries Many Potentially Harmful Recessive Mutations 699
GENETICS AS AN EXPERIMENTAL TOOL 699
The Classical Genetic Approach Begins with Mutagenesis 700
Conditional Mutants Permit the Study of Lethal Mutations 701
A Complementation Test Reveals Whether Two Mutations Are in the Same Gene
703
EXPLORING HUMAN GENETICS 704
Linked Blocks of Polymorphisms Have Been Passed Down from Our Ancestors
704
Polymorphisms Provide Clues to Our Evolutionary History 705
Genetic Studies Aid in the Search for the Causes of Human Diseases 706
Many Severe, Rare Human Diseases Are Caused by Mutations in Single Genes 706
Common Human Diseases Are Often Influenced by Multiple Mutations and
Environmental Factors 707

Genome-wide Association Studies Can Aid the Search for Mutations Associated
with Disease 708
We Still Have Much to Learn About the Genetic Basis of Human Variation and
Disease 709
ESSENTIAL CONCEPTS 712
QUESTIONS 713
CHAPTER 20
Cell Communities: Tissues, Stem Cells, and Cancer 717
EXTRACELLULAR MATRIX AND CONNECTIVE TISSUES 718
Plant Cells Have Tough External Walls 719
Cellulose Microfibrils Give the Plant Cell Wall Its Tensile Strength 720
Animal Connective Tissues Consist Largely of Extracellular Matrix 721
Collagen Provides Tensile Strength in Animal Connective Tissues 722
Cells Organize the Collagen They Secrete 724
Integrins Couple the Matrix Outside a Cell to the Cytoskeleton Inside It 724
Gels of Polysaccharides and Proteins Fill Spaces and Resist Compression 726
EPITHELIAL SHEETS AND CELL JUNCTIONS 728
Epithelial Sheets Are Polarized and Rest on a Basal Lamina 729
Tight Junctions Make an Epithelium Leakproof and Separate Its Apical and
Basolateral Surfaces 729
Cytoskeleton-linked Junctions Bind Epithelial Cells Robustly to One Another and
to the Basal Lamina 731
Gap Junctions Allow Cytosolic Inorganic Ions and Small Molecules to Pass from
Cell to Cell 733
STEM CELLS AND TISSUE RENEWAL 735
A Fertilized Egg Gives Rise to Every Cell Type and Tissue in the Body 735
Tissues Are Organized Mixtures of Many Cell Types 736
Different Tissues Are Renewed at Different Rates 738
Stem Cells and Proliferating Precursor Cells Generate a Continuous Supply of
Terminally Differentiated Cells 739
Specific Signals Maintain Stem-Cell Populations 741
Stem Cells Can Be Used to Repair Lost or Damaged Tissues 742
Induced Pluripotent Stem Cells Provide a Convenient Source of Human ES-like
Cells 743
Mouse and Human Pluripotent Stem Cells Can Form Organoids in Culture 744
CANCER 745
Cancer Cells Proliferate Excessively and Migrate Inappropriately 745
Epidemiological Studies Identify Preventable Causes of Cancer 746
Cancers Develop by an Accumulation of Somatic Mutations 747
Cancer Cells Evolve, Acquiring an Increasing Competitive Advantage 748
Two Main Classes of Genes Are Critical for Cancer: Oncogenes and Tumor
Suppressor Genes 751
Cancer-critical Mutations Cluster in a Few Fundamental Pathways 752
Colorectal Cancer Illustrates How Loss of a Tumor Suppressor Gene Can Lead to
Cancer 753
An Understanding of Cancer Cell Biology Opens the Way to New Treatments 754

ESSENTIAL CONCEPTS 756
QUESTIONS 760
ANSWERS A:1
GLOSSARY G:1
INDEX I:1

CHAPTER ONE 1
Cells: The Fundamental Units of Life
UNITY AND DIVERSITY OF CELLS
SEEING CELL STRUCTURE
THE TREE OF LIFE
THE EUKARYOTIC CELL
STUDYING MODEL SYSTEMS
What does it mean to be living? Petunias, people, and pond scum are all alive; stones, sand,
and summer breezes are not. But what are the fundamental properties that characterize living
things and distinguish them from nonliving matter?
The answer hinges on a basic fact that is taken for granted now but marked a revolution in
thinking when first established more than 175 years ago. All living things (or organisms) are
built from cells: small, membrane-enclosed units filled with a concentrated aqueous solution of
chemicals and endowed with the extraordinary ability to create copies of themselves by growing
and then dividing in two. The simplest forms of life are solitary cells. More complex organisms,
including ourselves, are communities of cells derived by growth and division from a single
founder cell. Every animal or plant is a vast colony of individual cells, each of which performs a
specialized function that is integrated by intricate systems of cell-to-cell communication.
Cells, therefore, are the fundamental units of life. Thus it is to cell biology—the study of cells
and their structure, function, and behavior—that we look for an answer to the question of what
life is and how it works. With a deeper understanding of cells, we can begin to tackle the grand
historical problems of life on Earth: its mysterious origins, its stunning diversity produced by
billions of years of evolution, and its invasion of every conceivable habitat on the planet. At the
same time, cell biology can provide us with answers to the questions we have about ourselves:
Where did we come from? How do we develop from a single fertilized egg cell? How is each of
us similar to—yet different from—everyone else on Earth? Why do we get sick, grow old, and
die?
In this chapter, we introduce the concept of cells: what they are, where they come from, and
how we have learned so much about them. We begin by looking at the great variety of forms that
cells can adopt, and we take a preliminary peek at the chemical machinery that all cells have in
common. We then consider how cells are made visible under the microscope and what we see
when we peer inside them. Finally, we discuss how we can exploit the similarities of living
things to achieve a coherent understanding of all forms of life on Earth—from the tiniest
bacterium to the mightiest oak.
Glossary
cell
The basic unit from which a living organism is made; an aqueous solution of chemicals,
enclosed by a membrane, that has an ability to self-replicate.

UNITY AND DIVERSITY OF CELLS
Biologists estimate that there may be as many as 100 million distinct species of living things
on our planet—organisms as different as a dolphin and a rose or a bacterium and a butterfly.
Cells, too, differ vastly in form and function. Animal cells differ from those in a plant, and even
cells within a single multicellular organism can differ wildly in appearance and activity. Yet
despite these differences, all cells share a fundamental chemistry and other common features.
In this section, we take stock of some of the similarities and differences among cells, and we
discuss how all present-day cells appear to have evolved from a common ancestral cell.
Cells Vary Enormously in Appearance and Function
When comparing one cell and another, one of the most obvious places to start is with size. A
bacterial cell—say a Lactobacillus in a piece of cheese—is a few micrometers, or μm, in length.
That’s about 25 times smaller than the width of a human hair. A frog egg, on the other hand, has
a diameter of about 1 millimeter (mm). If we scaled them up to make the Lactobacillus the size
of a person, the frog egg would be half a mile long. In fact, the eggs of most animals are giant,
single cells that contain a stockpile of nutrients that can support the growth of the embryo until it
hatches. A chicken egg is measured in centimeters—and the egg of an ostrich is more than 20
times that size.
Cells vary just as widely in their shape (Figure 1–1). A typical nerve cell in your brain, for
example, is enormously extended: it sends out its electrical signals along a single, fine protrusion
(an axon) that is 10,000 times longer than it is thick, and the cell receives signals from other
nerve cells through a collection of shorter extensions that sprout from its body like the branches
of a tree (Figure 1–1A). A pond-dwelling Paramecium, on the other hand, is shaped like a
submarine and is covered with thousands of cilia—hairlike projections whose sinuous,
coordinated beating sweeps the cell forward, rotating as it goes (Figure 1–1B). A cell in the
surface layer of a plant is squat and immobile, surrounded by a rigid box of cellulose with an
outer waterproof coating of wax (Figure 1–1C). A macrophage in the body of an animal, by
contrast, crawls through tissues, constantly pouring itself into new shapes, as it searches for and
engulfs debris, foreign microorganisms, and dead or dying cells (Figure 1–1D). A fission yeast is
shaped like a rod (Figure 1–1E), whereas a budding yeast is delightfully spherical (see Figure 1–
16). And so on.
Figure 1–1 Cells come in a variety of shapes and sizes. (A) Drawing of a single nerve

cell from a mammalian brain. This cell has a single, unbranched extension (axon),
projecting toward the top of the image, through which it sends electrical signals to other
nerve cells, and it possesses a huge branching tree of projections (dendrites) through which
it receives signals from as many as 100,000 other nerve cells. (B) Paramecium. This
protozoan—a single giant cell—swims by means of the beating cilia that cover its surface.
(C) The surface of a snapdragon flower petal displays an orderly array of tightly packed
cells. (D) A macrophage spreads itself out as it patrols animal tissues in search of invading
microorganisms. (E) A fission yeast is caught in the act of dividing in two. The medial
septum (stained red with a fluorescent dye) is forming a wall between the two nuclei (also
stained red ) that have been separated into the two daughter cells; in this image, the cells’
membranes are stained in patches with a green fluorescent dye. Note that the micrographs
have different scales: the nerve cell, with its sprawling extensions, is 100 times wider than
the fission yeast. (A, courtesy of Herederos de Santiago Ramón y Cajal, 1899; B, courtesy
of Anne Fleury, Michel Laurent, and André Adoutte; C, courtesy of Kim Findlay; D, from
P.J. Hanley et al., Proc. Natl. Acad. Sci. USA 107:12145–12150, 2010. With permission
from the National Academy of Sciences; E, courtesy of Janos Demeter and Shelley Sazer.)
Cells are also enormously diverse in their chemical requirements. Some require oxygen to
live; for others the gas is deadly. Some cells consume little more than carbon dioxide (CO 2 ),
sunlight, and water as their raw materials; others need a complex mixture of molecules produced
by other cells.
In multicellular organisms, these differences in size, shape, and chemical requirements
almost always reflect differences in cell function. Some cells operate as factories optimized for
the production of particular substances, such as hormones, starch, fat, latex, or pigments. Others,
like muscle cells, are engines that burn fuel to do mechanical work. Some cells can even generate
an electric current, like the stunningly specialized “electrocytes” of the electric eel.
QUESTION 1–1
“Life” is easy to recognize but difficult to define. According to one popular biology text,
living things:
1. Are highly organized compared to natural inanimate objects.
2. Display homeostasis, maintaining a relatively constant internal environment.
3. Reproduce themselves.
4. Grow and develop from simple beginnings.
5. Take energy and matter from the environment and transform it.
6. Respond to stimuli.
7. Show adaptation to their environment.
Score a person, a smartphone, and a potato with respect to these characteristics.
Some cells become so specialized that they cease to proliferate, thus producing no
descendants. Such a fate would be senseless for cells that live a solitary life. In a multicellular
organism, however, there is a division of labor among cells, allowing some cells to become
specialized to an extreme degree for particular tasks and leaving them dependent on their fellow
cells for many basic requirements. Even the most basic need of all, that of passing on the genetic

instructions of the organism to the next generation, is delegated to specialists: the egg and the
sperm.
Living Cells All Have a Similar Basic Chemistry
Despite the extraordinary diversity of plants and animals, people have recognized from time
immemorial that these organisms have something in common, something that entitles them all to
be called living things. But while it seemed easy enough to recognize life, it was remarkably
difficult to say in what sense all living things were alike. Textbooks had to settle for defining life
in abstract general terms related to growth, reproduction, and an ability to actively alter behavior
in response to the environment.

Figure 1–2 In all living cells, genetic information flows from DNA to RNA
(transcription) and from RNA to protein (translation)—a hierarchy known as the
central dogma. The sequence of nucleotides in a particular segment of DNA (a gene) is
transcribed into an RNA molecule, which can then be translated into the linear sequence of
amino acids of a protein. Only a small part of the gene, RNA, and protein is shown.
A profound yet elegant solution to this awkward situation has been provided by discoveries
in the fields of biochemistry and molecular biology. Although the cells of all living things are
enormously varied when viewed from the outside, they are fundamentally similar inside. We
now know that cells resemble one another to an astonishing degree in the details of their
chemistry. They are composed of the same sorts of molecules, which participate in the same

types of chemical reactions (discussed in Chapter 2). In all organisms, genetic information—in
the form of genes—is carried in DNA molecules. This information is written in the same
chemical code, constructed out of the same chemical building blocks, interpreted by essentially
the same chemical machinery, and replicated in the same way when a cell or organism
reproduces. Thus, in every cell, long polymer chains of DNA are made from the same set of four
monomers, called nucleotides, strung together in different sequences like the letters of an
alphabet. The information encoded in these DNA molecules is read out, or transcribed, into a
related set of polynucleotides called RNA. Although some of these RNA molecules have their
own regulatory, structural, or chemical activities, most are translated into a different type of
polymer called a protein. This flow of information—from DNA to RNA to protein—is so
fundamental to life that it is referred to as the central dogma (Figure 1–2).
At the same time, the appearance and behavior of a cell are dictated largely by its protein
molecules, which serve as structural supports, chemical catalysts, molecular motors, and much
more. Proteins are built from amino acids, and all organisms use the same set of 20 amino acids
to make their proteins. But the amino acids are linked in different sequences, giving each type of
protein molecule a different three-dimensional shape, or conformation, just as different
sequences of letters spell different words. In this way, the same basic biochemical machinery
supports and serves the full gamut of life on Earth (Figure 1–3).
(B)

(C)

(D)
Figure 1–3 All living organisms are constructed from cells. (A) A colony of bacteria, (B)
a butterfly, (C) a rose, and (D) a dolphin are all made of cells that have a fundamentally
similar chemistry and operate according to the same basic principles. (A, courtesy of Janice
Carr; D, courtesy of Jonathan Gordon, IFAW.)
Living Cells Are Self-replicating Collections of Catalysts
One of the most commonly cited properties of living things is their ability to reproduce. For
cells, the process involves duplicating their genetic material and other components and then
dividing in two—producing a pair of daughter cells that are themselves capable of undergoing
the same cycle of replication.
It is the special relationship between DNA, RNA, and proteins—reflected in the central
dogma (see Figure 1–2)—that makes this self-replication possible. DNA encodes information
that ultimately directs the assembly of proteins: the sequence of nucleotides in a molecule of
DNA dictates the sequence of amino acids in a protein. Proteins, in turn, catalyze the replication
of DNA and its transcription into RNA, and they participate in the translation of RNA into
proteins. This feedback loop between proteins and polynucleotides underlies the self-reproducing
behavior of living things (Figure 1–4). We discuss this complex interdependence between DNA,
RNA, and proteins in detail in Chapters 5 through 8.

Figure 1–4 Life is an autocatalytic process. DNA and RNA provide the sequence
information (green arrows) that is used to produce proteins and to copy themselves.
Proteins, in turn, provide the catalytic activity (red arrows) needed to synthesize DNA,
RNA, and themselves. Black arrows represent the biochemical processes by which new
DNA, RNA, and proteins are manufactured in cells. Together, these feedback loops create
the self-replicating system that endows living cells with their ability to reproduce.
In addition to their roles in polynucleotide and protein synthesis, proteins also catalyze the
many other chemical reactions that keep the self-replicating system shown in Figure 1–4
running. A living cell can break down nutrients and use the products both to make the building
blocks needed to produce polynucleotides, proteins, and other cell constituents and to generate
the energy needed to power these biosynthetic processes. We discuss these vital metabolic
reactions in detail in Chapters 3 and 13.
Only living cells can perform these astonishing feats of self-replication. Viruses, which are
little more than DNA or RNA wrapped in a protective coat, do not have the ability to reproduce
by their own efforts. Instead, they parasitize the reproductive machinery of the cells that they
invade to make copies of themselves. Without a host cell to aid them, viruses are inert and,
therefore, are not generally considered to be living. Unfortunately for us, these genetic zombies
are not entirely harmless: once viruses gain entry, they can exert a malign influence over a cell—
or an organism, as demonstrated by the coronavirus responsible for the COVID-19 pandemic
(discussed later in this chapter and in Chapter 9).
All Living Cells Have Apparently Evolved from the Same
Ancestral Cell
When a cell replicates its DNA in preparation for cell division, the copying is not always
perfect. On occasion, the instructions are misread or become damaged by mutations that change
the sequence of nucleotides in the DNA. For this reason, daughter cells are not necessarily exact
replicas of their parent.
Mutations can create offspring that are changed for the worse (in that they are less able to
survive and reproduce), changed for the better (in that they are better able to survive and
reproduce), or changed in a neutral way (in that they are genetically different but equally viable).
The struggle for survival eliminates the first, favors the second, and tolerates the third. The genes
of the next generation will be the genes of the survivors.

QUESTION 1–2
Mutations are mistakes in the DNA that change the genetic plan from that of the previous
generation. Imagine a shoe factory. Would you expect mistakes (i.e., unintentional changes) in
copying the shoe design to lead to improvements in the shoes produced? Explain your answer.
For many organisms, the pattern of heredity is further complicated by sexual reproduction, in
which two cells of the same species fuse, pooling their DNA. In the process, the genes from each
parent are combined and then distributed in new combinations to the next generation, to be tested
again for their ability to promote survival and reproduction. We discuss the mechanism of this
genetic shuffling in Chapter 19.
These simple principles of genetic change and selection, applied repeatedly over billions of
cell generations, are the basis of evolution—the process by which living species become
gradually modified and adapted to their environment in more and more sophisticated ways.
Evolution offers a startling but compelling explanation of why present-day cells are so similar in
their fundamentals: they have all inherited their genetic instructions from the same common
ancestral cell. It is estimated that this cell existed between 3.5 and 3.8 billion years ago, and we
must suppose that it contained a prototype of the molecular machinery used by all life on Earth
today. Through a very long process of mutation and natural selection, the descendants of this
ancestral cell have gradually diverged to fill every habitat on Earth with organisms that exploit
the potential of this universal machinery in a seemingly endless variety of ways.
Genes Provide Instructions for the Form, Function, and
Behavior of Cells and Organisms
A cell’s genome—that is, the entire sequence of nucleotides in an organism’s DNA—
provides a genetic program that instructs a cell how to function. For the cells of plant and animal
embryos, the genome directs the growth and development of an adult organism with hundreds of
different cell types. Within an individual plant or animal, these cells can be extraordinarily
varied, as we discuss in detail in Chapter 20. Fat cells, skin cells, bone cells, and nerve cells
seem as dissimilar as any cells could be. Yet all these differentiated cell types are generated
during embryonic development from a single fertilized egg, and they contain identical copies of
the DNA of that individual. Their varied characters stem from the way that individual cells use
their genetic instructions (see Movie 1.1). Different cells express different genes: that is, they use
their genes to produce some RNAs and proteins and not others, depending on their identity, their
current state, and on cues that they and their progenitors have received from their surroundings—
mainly in the form of signals from other cells in the organism.
The DNA, therefore, is not just a shopping list specifying the molecules that every cell must
make, and a cell is not just an assembly of all the items on the list. Each cell is capable of
carrying out a variety of biological tasks, depending on its environment and its history, and it
selectively uses the information encoded in its DNA to guide its activities. Later in this book, we
will see in detail how DNA defines both the parts list of the cell and the rules that decide which
cells receive which parts.
Glossary

micrometer
Unit of length equal to one millionth (10 –6 ) of a meter or 10 –4 centimeter.
DNA
Double-stranded polynucleotide formed from two separate chains of covalently linked
deoxyribonucleotides. It serves as the cell’s store of genetic information that is transmitted
from generation to generation.
RNA (ribonucleic acid)
Molecule produced by the transcription of DNA; usually single-stranded, it is a
polynucleotide composed of covalently linked ribonucleotide subunits. Serves a variety of
informational, structural, catalytic, and regulatory functions in cells.
protein
Macromolecule built from amino acids that provides cells with their shape and structure
and performs most of their activities.
evolution
Process of gradual modification and adaptation that occurs in living organisms over
generations.
genome
The total genetic information carried by all the chromosomes of a cell or organism; in
humans, the total number of nucleotide pairs in the 22 autosomes plus the X and Y
chromosomes.

SEEING CELL STRUCTURE
Today, we have access to many powerful technologies for deciphering the principles that
govern cell structure and activity. But the earliest cell biologists began their explorations by
simply looking at tissues and cells. Over time, they would try to break cells open or slice tissues
thinly enough to reveal their contents. The results of these pioneering efforts must initially have
been baffling. What would budding cell biologists have made of this collection of tiny whorls
and discs and blobs—objects whose relationship to the properties of living matter no doubt
seemed an impenetrable mystery? It would take decades—even centuries—of additional
investigation to unravel the sophisticated functions of these mysterious cell structures.
Nevertheless, it was the visual investigation of biological materials that served as the first step
toward understanding the workings of cells and tissues, and this approach remains essential in
modern studies of cell biology.
Cells themselves were not seen directly until the seventeenth century, when the instrument
we call a microscope was invented. For hundreds of years afterward, everything that was known
about cells was discovered using this device. Light microscopes use visible light to illuminate
specimens, and they allowed biologists to view for the first time the intricate and interdependent
structures that provide the foundation for all living things.
Although these instruments now incorporate many sophisticated improvements, the
properties of light—specifically its wavelength—limit the fineness of detail these microscopes
reveal: it is simply not possible, using visible light, to distinguish objects beyond a certain
resolution. Electron microscopes, invented in the 1930s, go beyond this limit by using beams of
electrons instead of beams of light as the source of illumination; because electrons have a much
shorter wavelength, these instruments greatly extend our ability to see the fine details of cell
structure and even render some of its larger molecules visible individually.
In this section, we describe various forms of light and electron microscopy. These vital tools
in the modern cell biology laboratory continue to improve, revealing new and sometimes
surprising details about how cells are built and how they operate.
The Invention of the Light Microscope Led to the
Discovery of Cells
By the seventeenth century, glass lenses were powerful enough to permit the detection of
structures invisible to the naked eye. Using an instrument equipped with such a lens, Robert
Hooke examined a piece of cork and in 1665 reported to the Royal Society of London that the
cork was composed of a mass of minuscule chambers. He called these chambers “cells,” based
on their resemblance to the simple rooms occupied by monks in a monastery. The name stuck,
even though the structures Hooke described were actually the cell walls that remained after the
plant cells living inside them had died. But it didn’t take long for Hooke and other early
microscopists to spy, for the very first time, a variety of living cell types. Dutch scientist Antonie
van Leeuwenhoek, for example, discovered that even a single drop of pond water contains a
previously unseen world teeming with tiny creatures—twirling, tumbling, and occasionally
oozing along as they went about the business of being alive.

QUESTION 1–3
You have embarked on an ambitious research project: to create life in a test tube. You boil up
a rich mixture of yeast extract and amino acids in a flask, along with a sprinkling of the inorganic
salts known to be essential for life. You seal the flask and allow it to cool. After several months,
the liquid is as clear as ever, and there are no signs of life. A friend suggests that excluding the
air was a mistake, since most life as we know it requires oxygen. You repeat the experiment, but
this time you leave the flask open to the atmosphere. To your great delight, the liquid becomes
cloudy after a few days, and, under the microscope, you see beautiful little cells that are actively
growing and dividing. Does this experiment prove that you somehow managed to create life
from inanimate materials? How might you redesign your experiment to allow air into the flask,
yet eliminate the possibility that contamination by airborne microorganisms is the explanation
for the results? (For a ready-made answer, look up the classic experiments of Louis Pasteur.)
For almost 200 years, light microscopes remained exotic devices, available only to a few
wealthy individuals. It was not until the nineteenth century that microscopes began to be used
widely to look at cells. The emergence of cell biology as a distinct science was a gradual process
to which many individuals contributed, but its official birth is generally said to have been
signaled by two publications: one by the botanist Matthias Schleiden in 1838 and the other by the
zoologist Theodor Schwann in 1839. In these papers, Schleiden and Schwann documented the
results of a systematic investigation of plant and animal tissues with the light microscope,
showing that cells were the universal building blocks of all living tissues. Their work, and that of
other nineteenth-century microscopists, slowly led to the realization that all living cells are
formed by the growth and division of preexisting cells—a principle sometimes referred to as the
cell theory (Figure 1–5). The implication that living organisms do not arise spontaneously but
can be generated only from preexisting organisms was hotly contested, but it was finally
confirmed in the 1860s by an elegant set of experiments performed by Louis Pasteur (see
Question 1–3).
Figure 1–5 New cells form by growth and division of preexisting cells. (A) In 1880,
Eduard Strasburger drew a living plant cell (a hair cell from the common spiderwort,
Tradescantia virginiana), which he observed dividing in two over a period of 2.5
hours. Inside the cell, DNA (black) can be seen condensing into chromosomes, which
are then segregated into the two daughter cells. (B) A comparable living plant cell
photographed through a modern light microscope. (B, from P.K. Hepler, J. Cell Biol.

100:1363–1368, 1985. With permission from Rockefeller University Press.)
The principle that cells are generated only from preexisting cells and inherit their
characteristics from them underlies all of biology and gives the subject a unique flavor: in
biology, questions about the present are inescapably linked to conditions in the past. To
understand why present-day cells and organisms behave as they do, we need to understand their
history, all the way back to the misty origins of the first cells on Earth. Charles Darwin provided
the key insight that makes this history comprehensible. His theory of evolution, published in
1859, explains how random variation and natural selection gave rise to diversity among
organisms that share a common ancestry. When combined with the cell theory, the theory of
evolution leads us to view all life, from its beginnings to the present day, as one vast family tree
of individual cells. Although this book is primarily about how cells work today, we will
encounter the theme of evolution again and again, because evolution explains how cells acquired
their characteristic features.
Light Microscopes Reveal Some of a Cell’s Components
If a very thin slice is cut from a suitable plant or animal tissue and viewed using a light
microscope, it is immediately apparent that the tissue is divided into thousands of small cells. In
some cases, the cells are closely packed; in others, they are separated from one another by an
extracellular matrix—a dense material often made of protein fibers embedded in a gel of long
sugar chains. Each cell is typically about 5–20 μm in diameter. If care has been taken to keep the
specimen alive, particles will be seen moving around inside its individual cells. On occasion, a
cell may even be seen slowly changing shape and dividing into two (see Figure 1–5).
Distinguishing the internal structure of a cell is difficult, not only because the parts are small,
but also because they are transparent and mostly colorless. One way around the problem is to
stain cells with dyes that color particular components differently (Figure 1–6). Alternatively, one
can exploit the fact that cell components differ slightly from one another in refractive index, just
as glass differs in refractive index from water, causing light rays to be deflected as they pass
from the one medium into the other. The small differences in refractive index can be made
visible by specialized optical techniques, and the resulting images can be enhanced further by
electronic processing (Figure 1–7A).

Figure 1–6 Cells form tissues in plants and animals. (A) Cells in the root tip of a
fern. The DNA-containing nuclei are stained red, and each cell is surrounded by a thin
cell wall (light blue). The cells at the bottom corners of the preparation are so densely

packed that only the red nuclei are readily visible. (B) Cells in the urine-collecting
ducts of a human kidney. Each duct appears in this cross section as a ring of closely
packed cells (with nuclei stained dark blue). The rings are surrounded by extracellular
matrix, stained light purple, which contains the scattered cells that produced most of
the matrix components. (A, courtesy of James Mauseth; B, Jose Luis
Calvo/Shutterstock.)

Figure 1–7 Some of the internal structures of a cell can be seen with a light
microscope. (A) A cell taken from human skin and grown in culture was photographed
through a light microscope using interference-contrast optics (described in Panel 1–1, pp.
12–13). The nucleus is especially prominent, as is the small, round nucleolus within it
(discussed in Chapter 5; and see Panel 1–2, p. 27). (B) A pigment cell from a frog, stained
with fluorescent dyes and viewed with a confocal fluorescence microscope (discussed in
Panel 1–1). The nucleus is shown in purple, the pigment granules in red, and the
microtubules—a class of protein filaments in the cytoplasm—in green. (A, courtesy of
Casey Cunningham; B, courtesy of Stephen Rogers and the Imaging Technology Group of
the Beckman Institute, University of Illinois, Urbana.)
As shown in Figure 1–6B and Figure 1–7A, typical animal cells visualized in these ways
have a distinct anatomy. They have a sharply defined boundary, indicating the presence of an
enclosing membrane, the plasma membrane. A large, round structure, the nucleus, is prominent
near the middle of the cell. Around the nucleus and filling the cell’s interior is the cytoplasm, a
transparent substance crammed with what seems at first to be a jumble of miscellaneous objects.
With a good light microscope, one can begin to distinguish and classify some of the specific
components in the cytoplasm, but structures smaller than about 0.2 μm—about half the
wavelength of visible light—cannot normally be resolved; in other words, they cannot be
distinguished from the objects that surround them and appear as a single blur.
In recent years, however, new types of light microscope called fluorescence microscopes
have been developed that use sophisticated methods of illumination and electronic image
processing to see fluorescently labeled cell components in much finer detail (Figure 1–7B). The
most recent superresolution fluorescence microscopes, for example, can push the limits of
resolution down even further, to about 20 nanometers (nm). That is the size of a single ribosome,
the large macromolecular complex that translates RNAs into proteins. These superresolution
techniques are described further in Panel 1–1 (pp. 12–13).
The Fine Structure of a Cell Is Revealed by Electron
Microscopy

For the highest magnification and best resolution, one must turn to an electron microscope,
which can reveal details down to a few nanometers. Preparing cell samples for the electron
microscope is a painstaking process. Even for light microscopy, a tissue often has to be fixed
(that is, preserved by pickling in a reactive chemical solution), supported by embedding in a solid
wax or resin, cut, or sectioned, into thin slices, and stained before it is viewed. (The tissues in
Figure 1–6 were prepared in this way.) For electron microscopy, similar procedures are required,
but the sections have to be much thinner and there is no possibility of looking at living cells.
When thin sections are cut, stained with electron-dense heavy metals, and placed in the
electron microscope, much of the jumble of cell components becomes sharply resolved into
distinct organelles—separate, recognizable substructures with specialized functions that are often
only hazily defined with a conventional light microscope. The delicate plasma membrane can be
seen surrounding the cell, and similar membranes, called internal membranes, form distinct
boundaries around many of the organelles inside (Figure 1–8A and B). All of these membranes
are only about 5 nm—or two molecules—thick (as discussed in Chapter 11). When the
resolution of the electron microscope is pushed, even individual large molecules can readily be
seen (Figure 1–8C).
Figure 1–8 The fine structure of a cell can be seen in a transmission electron
microscope. (A) Thin section of a liver cell, showing the enormous amount of detail that is
visible. Some of the components to be discussed later in this chapter are labeled; they are

identifiable by their size, location, and shape. (B) A small region of the cytoplasm at higher
magnification. The smallest structures that are clearly visible are the ribosomes, each of
which is made of 80–90 or so individual protein and RNA molecules; some of the
ribosomes are free in the cytoplasm, while others are bound to a membrane-enclosed
organelle—the endoplasmic reticulum—discussed later (see Figure 1–23). (C) Portion of a
long, threadlike DNA molecule isolated from a cell and viewed by electron microscopy.
The DNA has been artificially thickened to enhance its visibility. (A and B, by permission
of E.L. Bearer and Daniel S. Friend; C, courtesy of Mei Lie Wong.)
The type of electron microscope used to look at thin sections of tissue is known as a
transmission electron microscope. This instrument is, in principle, similar to a light microscope,
except that it transmits a beam of electrons rather than a beam of light through the sample.
Another type of electron microscope—the scanning electron microscope—scatters electrons off
the surface of the sample and so is used to look at the surface detail of cells and other structures.
These techniques, along with the different forms of light microscopy, are reviewed in Panel 1–1
(pp. 12–13).
Most conventional electron microscopes cannot visualize the individual atoms that make up
biological molecules (Figure 1–9). To study the cell’s key components in atomic detail,
biologists have developed even more sophisticated tools. Techniques such as x-ray
crystallography or an enhanced form of electron microscopy called cryo-electron microscopy, for
example, can be used to determine the precise positioning of atoms within the three-dimensional
structure of protein molecules and complexes (discussed in Chapter 4).
Figure 1–9 How big are cells and their components? (A) This chart lists sizes of cells

and their component parts, the units in which they are measured, and the instruments needed
to visualize them. (B) Drawings convey a sense of scale between living cells and atoms.
Each panel shows an image that is magnified by a factor of 10 compared to its predecessor
—producing an imaginary progression from a thumb, to skin, to skin cells, to a
mitochondrion, to a ribosome, and ultimately to a cluster of atoms forming part of one of the
many protein molecules in our bodies. Note that ribosomes are present inside mitochondria
(as shown here), as well as in the cytoplasm.
PANEL 1–1 MICROSCOPY
CONVENTIONAL LIGHT MICROSCOPY

A conventional light microscope allows us to magnify cells up to 1000 times and to resolve
details as small as 0.2 μm (200 nm), a limitation imposed by the wavelength of light, not by the
quality of the lenses. Three things are required for viewing cells in a light microscope. First, a
bright light must be focused onto the specimen by lenses in the condenser. Second, the specimen
must be carefully prepared to allow light to pass through it. Third, an appropriate set of lenses
(objective, tube, and eyepiece) must be arranged to focus an image of the specimen in the eye.
LOOKING AT UNSTAINED SAMPLES

The same unstained animal cell (a fibroblast) viewed with
(A) the simplest, bright-field optics;
(B) phase-contrast optics;
(C) interference-contrast optics.
The two latter systems exploit differences in the way light travels through regions of the cell
with differing refractive indices. All three images can be obtained on the same microscope
simply by interchanging optical components.
FIXED SAMPLES

Most tissues are neither small enough nor transparent enough to examine directly in the
microscope. Typically, therefore, they are chemically fixed and cut into thin slices, or sections,
that can be mounted on a glass microscope slide and subsequently stained to reveal different
components of the cells. A stained section of a plant root tip is shown here (D).
FLUORESCENCE MICROSCOPY

Fluorescent dyes used for staining cells are detected with the aid of a fluorescence
microscope. This setup is similar to an ordinary light microscope, except that the illuminating
light is passed through two sets of filters (yellow). The first (1) filters the light before it reaches
the specimen, passing only those wavelengths that excite the particular fluorescent dye. The
second (2) blocks out this light and passes only those wavelengths emitted when the dye
fluoresces. Dyed objects show up in bright color on a dark background.
FLUORESCENT PROBES

Fluorescent molecules absorb light at one wavelength and emit it at another, longer
wavelength. Some fluorescent dyes bind specifically to particular molecules in cells and can
reveal their location when the cells are examined with a fluorescence microscope. In these
dividing nuclei in a fly embryo, the stain for DNA fluoresces blue. Other dyes can be coupled to
antibody molecules, which then serve as highly specific staining reagents that bind selectively to
particular molecules, showing their distribution in the cell. Because fluorescent dyes emit light,
they allow objects even smaller than 0.2 μm to be seen. Here, microtubule proteins in the mitotic
spindle (see Figure 1–29) are stained green with a fluorescent antibody.
CONFOCAL FLUORESCENCE MICROSCOPY

A confocal microscope is a specialized type of fluorescence microscope that builds up an
image by scanning the specimen with a laser beam. The beam is focused onto a single point at a
specific depth in the specimen, and a pinhole aperture in the detector allows only fluorescence
emitted from this point to be included in the image. Scanning the beam across the specimen
generates a sharp image of the plane of focus—an optical section. A series of optical sections at
different depths are then combined to form a three-dimensional image, such as this highly
branched mitochondrion in a living yeast cell.
SUPERRESOLUTION FLUORESCENCE MICROSCOPY
Recently, several ingenious technical advances have allowed fluorescence microscopes to
break the usual resolution limit of 200 nm. One such technique uses a sample that is labeled with
molecules whose fluorescence can be reversibly switched on and off by different colored lasers.
The specimen is scanned by a nested set of two laser beams, in which the central beam excites
fluorescence in a very small spot of the sample, while a second beam—wrapped around the first
—switches off fluorescence in the surrounding area. A related approach allows the positions of
individual fluorescent molecules to be accurately mapped while others nearby are switched off.
Both approaches slowly build up an image with a resolution as low as 20 nm. These new super
resolution methods are being extended into 3-D imaging and real-time live cell imaging.

Microtubules viewed with conventional fluorescence microscope (left) and with
superresolution optics (right). In the superresolution image, the microtubules can be clearly
seen; their actual size is only 25 nm in diameter.
TRANSMISSION ELECTRON MICROSCOPY

The electron micrograph below shows a small region of a cell in a thin section of testis. The
tissue has been chemically fixed, embedded in plastic, and cut into very thin sections that have
then been stained with salts of uranium and lead.

The transmission electron microscope (TEM) is in principle similar to a light microscope, but
it uses a beam of electrons instead of a beam of light, and magnetic coils to focus the beam
instead of glass lenses. Because the wavelength of electrons is so short, the resolution is greatly
increased, but the specimen must be very thin. Contrast is usually introduced by staining the
specimen with electron-dense heavy metals. The specimen is then placed in a vacuum in the
microscope. The TEM has a useful magnification of up to a million-fold and can resolve details
as small as about 1 nm in biological specimens.
SCANNING ELECTRON MICROSCOPY

In the scanning electron microscope (SEM), the specimen, which has been coated with a very
thin film of a heavy metal, is scanned by a beam of electrons brought to a focus on the specimen
by magnetic coils that act as lenses. The quantity of electrons scattered or emitted as the beam
bombards each successive point on the surface of the specimen is measured by the detector, and
is used to control the intensity of successive points in an image built up on a video screen. The
microscope creates striking images of three-dimensional objects with great depth of focus and
can resolve details between 3 nm and 20 nm, depending on the instrument.

Scanning electron micrograph of stereocilia projecting from a hair cell in the inner ear
(left). For comparison, the same structure is shown by light microscopy, at the limit of its
resolution (above).
Glossary
microscope
Instrument for viewing extremely small objects. Some use a focused beam of visible
light and are used to examine cells and organelles. Others use a beam of electrons and can
be used to examine objects as small as individual molecules.
plasma membrane
The protein-containing lipid bilayer that surrounds a living cell.
cytoplasm
Contents of a cell that are contained within its plasma membrane but, in the case of
eukaryotic cells, outside the nucleus.
fluorescence microscope
Instrument used to visualize a specimen that has been labeled with a fluorescent dye;
samples are illuminated with a wavelength of light that excites the dye, causing it to
fluoresce.
ribosome

Large macromolecular complex, composed of RNAs and proteins, that translates a
messenger RNA into a polypeptide chain.
electron microscope
Instrument that passes a beam of electrons through the specimen to reveal and magnify
the structures of very small objects, such as organelles and large molecules.
organelle
A discrete structure or subcompartment of a eukaryotic cell that is specialized to carry
out a particular function. Examples include mitochondria and the Golgi apparatus.

THE TREE OF LIFE
When Darwin returned from his expedition on the HMS Beagle, he sketched in a notebook a
simple tree—above which he jotted the phrase, “I think.” The concept he was attempting to think
through was that of evolution: the idea that all living species arise from common ancestors, like
twigs that bud from existing tree branches. Some of these twigs are strong and vigorous, and they
grow into great branches from which new twigs—or species—will sprout; others die and fall to
the ground, like species that go extinct but leave behind remains that are preserved in the fossil
record. Although each branch of this tree is unique, all are related and form a family tree that
connects the explosion of life forms that have spread across our planet and—as Darwin wrote in
The Origin of Species—”covers the surface with its ever branching and beautiful ramifications.”
In this section, we outline—in broad terms—the diversity of organisms on our planet. We
discuss the defining characteristics that distinguish the major branches of life’s family tree and
offer a brief description of the lifestyles and lineages of the organisms that constitute each of
these divisions. Because the genetic blueprints for all of these organisms are written in the
universal language of DNA—information that modern sequencing methods allow us to easily
read—we now have the ability to accurately characterize and catalog the ways in which living
things differ and the ways in which they are alike. By studying these relationships, we can begin
to assign every organism—the ones alive today and those that lived in the past—its proper place
on the tree of life.
The Tree of Life Has Three Major Divisions
For most of human history, the living world was classified on the basis of outward
appearances. A fish has jaws, eyes, a backbone, and brain; humans do, too—but a worm does
not. A rosebush looks more like an apple tree than it does a blade of grass. Characterizing such
visible features is certainly a good place to begin a study of the natural world. Such observations
are what pointed Darwin toward his revolutionary theory of evolution.
But as the differences between organisms become larger, their relationships become harder to
decipher. Is the fuzzy mold growing in that jar of jam more like a sunflower or a snow leopard?
Is a shark more closely related to a starfish or a sperm whale? And what happens when
organisms look remarkably similar? When it comes to bacteria, for example, one tiny rod-shaped
cell can be almost impossible to distinguish from another—at least by sight.
The solution lies in their shared chemistry: because all organisms store genetic information in
the form of DNA, analyzing the genome of an organism provides a simple yet powerful way to
assess its kinship. The complete genome sequences of thousands of different organisms have
been collected and are stored in publicly accessible databases. With the help of computers, DNA
sequences from one organism can be quickly and easily compared to that of any other. Because
DNA is subject to random mutations that alter these sequences, examining the differences
between the DNA sequences of any two organisms can provide a direct measure of the
evolutionary distance that separates them, a topic we revisit in greater depth in Chapter 9.
This approach has revealed that the living world consists of three major divisions, or
domains: eukaryotes, bacteria, and archaea (Figure 1–10). Although eukaryotes are the main
focus of this book, in terms of genetic diversity, they constitute the smallest domain within this

elaborate, sequence-based tree.
Figure 1–10 Genome sequence comparisons produce a family tree of life that
contains three major divisions. All organisms on Earth can be assigned to one of these
domains: bacteria, archaea, and eukaryotes. Of the three domains, bacteria (blue) encompass
by far the greatest diversity, commensurate with their ability to colonize nearly every
ecological niche on the planet. So many new species of bacteria and archaea (yellow) are
being discovered through DNA sequencing of environmental samples that many do not yet
have names. Eukaryotes (pink) form a remarkably small slice of overall global diversity—
and given their close kinship with archaea, some scientists have proposed combining
eukaryotes and archaea into a single domain. In this diagram, the lengths of the branches are
proportional to the differences among genomes as assessed by sequencing common genes
that can be recognized and compared across many different species (discussed in Chapter
9). The tips of these branches represent individual species, but for clarity, only a small
subset of Earth’s species is displayed. Some of the organisms discussed in this chapter and
throughout the book are indicated. (Adapted from C.J. Castelle and J.F. Banfield, Cell
172:1181–1197, 2018.)
Eukaryotes Comprise the Domain of Life Most Familiar
to Us
The living things we see around us every day are eukaryotes—from the flowers that bloom in
our gardens to the face that gazes back at us from the mirror each day. The name comes from the

Greek words eu, meaning “well” or “truly,” and karyon, a “kernel” or “nucleus.” Eukaryotic
cells store their DNA in a membrane-enclosed organelle called the nucleus. Because this
structure can be seen using a light microscope, its presence (or absence) was an obvious and
simple way to begin to classify living organisms: those possessing a nucleus were called
eukaryotes and those lacking a nucleus were called prokaryotes (from the Greek pro, meaning
“before”). Thanks to DNA sequencing, we now know that the world of prokaryotes actually
includes both bacteria and archaea—the other two domains of life.
Eukaryotic cells are typically much larger than those of bacteria and archaea. Their genomes
run much larger, too: humans and corals each have more than 20,000 genes, whereas the
bacterium Escherichia coli operates on a mere 4300.
Although we often think of animals when we contemplate eukaryotes (perhaps because we
are animals, too), an astonishing array of single-celled, microscopic life forms are also
eukaryotic—including many of the pond-dwelling creatures that entertained van Leeuwenhoek
centuries ago. The eukaryotic family also includes fungi (such as mushrooms and the yeasts we
use to make beer and bread) and plants. In fact, most of Earth’s biomass is found in plants. DNA
sequencing, combined with other advanced techniques, suggests that our planet supports some
550 gigatons of carbon—carbon being the element on which the chemistry of life is based, as we
discuss in Chapter 2. Although we usually measure chemicals in very small amounts—grams or
even milligrams or micrograms—the amount of carbon on the planet is unimaginably large: a
single gigaton is equal to 10 15 grams. (If an elephant has a mass of about 5 × 10 6 grams, 1
gigaton would be the equivalent of 200,000,000 elephants!) Of the more than 500 gigatons of
carbon on Earth, 70 gigatons is found in bacteria, 7 gigatons in archaea, and a whopping 450
gigatons in plants. Animals constitute only 2 gigatons of Earth’s biomass—a number that is
humbling.
Bacteria Comprise the Most Diverse Collection of
Organisms on Earth
In reconstructing the tree of life based on DNA sequences, one of the biggest surprises was
how much more evolutionarily diverse the world of bacteria is compared to that of eukaryotes.
We now know that this immense diversity reflects the early appearance of bacteria in the
evolutionary history of the planet: evidence suggests that bacteria have been around for at least
3.5 billion years, since Earth was in its infancy.
Bacteria (singular, bacterium) are generally very small: only a few micrometers long, they
are invisible to the naked eye. Most live as single-celled organisms, although some join together
to form chains, clusters, or other organized, multicellular structures. Bacteria are typically
spherical, rodlike, or corkscrew-shaped (Figure 1–11). They often have a tough protective coat,
or cell wall, surrounding the plasma membrane, which encloses a single compartment containing
the cytoplasm and the DNA. Viewed with an electron microscope, the cell interior typically
appears as a matrix of varying texture, without any obvious organized internal structure (Figure
1–12).

Figure 1–11 Bacteria come in different shapes and sizes. Typical spherical, rodlike,
and spiral-shaped bacteria are drawn to scale. The spiral cells shown are the organisms that
cause syphilis.
Figure 1–12 The bacterium Escherichia coli (E. coli) has served as an important
model organism. An electron micrograph of a longitudinal section is shown here; the cell’s
DNA is concentrated in the lightly stained region. Note that E. coli has an outer membrane
and an inner (plasma) membrane, with a thin cell wall in between. The many flagella
distributed over its surface are not visible in this micrograph. (Courtesy of E. Kellenberger.)
QUESTION 1–4
A bacterium weighs about 10 –12 g and can divide every 20 minutes. If a single bacterial cell
carried on dividing at this rate, how long would it take before the mass of bacteria would equal
that of the Earth (6 × 10 24 kg)? Contrast your result with the fact that bacteria originated at least
3.5 billion years ago and have been dividing ever since. Explain the apparent paradox. (The
number of cells N in a culture at time t is described by the equation N = N 0 × 2 t/G , where N 0 is the
number of cells at zero time, and G is the time it takes for the population to double in size.)

Although simple in shape and structure, in terms of their chemistry bacteria are incredibly
sophisticated. Some are aerobic, using oxygen to oxidize food molecules; some are strictly
anaerobic and are killed by the slightest exposure to oxygen. Virtually any organic, carboncontaining
material—from wood to petroleum—can be used as food by one sort of bacterium or
another. Even more remarkably, some can live entirely on inorganic substances: they can get
their carbon from CO 2 in the atmosphere, their nitrogen from atmospheric N 2 , and their oxygen,
hydrogen, sulfur, and phosphorus from air, water, and inorganic minerals. Some of these bacteria
perform photosynthesis, using energy from sunlight to produce organic molecules from CO 2 , a
strategy we commonly associate with plants (Figure 1–13); others derive energy from the
chemical reactivity of inorganic substances in the environment (Figure 1–14). In either case,
such bacteria play a unique and fundamental part in the nutritional “economics” of life on Earth,
as other living organisms depend on the organic compounds that these versatile cells generate
from inorganic materials.
Figure 1–13 Some bacteria are photosynthetic. (A) Anabaena cylindrica forms long,
multicellular chains. This light micrograph shows specialized cells that either fix
nitrogen (that is, capture N 2 from the atmosphere and incorporate it into organic
compounds; labeled H), fix CO 2 through photosynthesis (labeled V), or become
resistant spores (labeled S) that can survive under unfavorable conditions. (B) An
electron micrograph of a related species, Phormidium laminosum, shows the
intracellular membranes where photosynthesis occurs. As shown in these micrographs,
some prokaryotes can have intracellular membranes and form simple multicellular
organisms. (A, courtesy of David Adams; B, courtesy of D.P. Hill and C.J. Howe.)

Figure 1–14 A sulfur bacterium gets its energy from hydrogen sulfide (H 2 S).
Beggiatoa, a bacterium that lives in sulfurous environments, oxidizes H 2 S to produce sulfur
and can fix carbon even in the dark. In this light micrograph, yellow deposits of sulfur can
be seen inside two of these bacterial cells. (Courtesy of Ralph W. Wolfe.)
Bacteria also exploit an enormous range of habitats, from the hot springs in Yellowstone
National Park to the insides of other living cells and organisms. Some of these relationships are
harmful. In the Middle Ages, bacteria that caused the bubonic plague wiped out half the
population of Europe; today, different bacteria cause a variety of human diseases from cholera

and whooping cough to tuberculosis. But some bacteria are actually beneficial. Thousands of
different bacterial species reside on our skin and in our gut, where they promote a healthy
immune response. And as we discuss later in this chapter, mitochondria—the organelles that
generate energy in eukaryotic cells—are thought to have evolved from aerobic bacteria that took
to living inside an anaerobic ancestral cell. Thus our own metabolism can be regarded as a
product of the activity of an organelle whose evolutionary birthright we can trace to a bacterial
cell.
Bacteria vastly outnumber all eukaryotic organisms on Earth not only because they are small
and have been around for much longer, but because they reproduce so quickly. Under optimum
conditions, when food is plentiful, a bacterial cell can divide in two about every 20 minutes. In
only 11 hours, a single bacterium can therefore give rise to more than 8 billion progeny (which
exceeds the total number of people currently on Earth). Thanks to their large numbers, rapid
proliferation, and ability to exchange bits of genetic material by a process akin to sex, bacterial
populations can evolve fast, rapidly acquiring the ability to use a new food source or to resist
being killed by a new antibiotic (as we discuss in Chapter 9).
The World of Archaea Is the Most Mysterious of Life’s
Domains
Of the three domains of life, that of archaea (singular, archaeon) remains the most poorly
understood. Most of its members have been identified only by DNA sequencing of
environmental samples, including those skimmed from the ocean surface or hauled up from the
boiling hot hydrothermal vents that penetrate Earth’s crust along the darkest depths of the ocean
floor. Like bacteria, the archaea we know most about are small and lack the internal, membraneenclosed
organelles that distinguish the eukaryotes. But archaea also differ from bacteria in many
ways, including the chemistry of their cell walls, the types of lipids that make up their
membrane, and the range of chemical reactions they can carry out.

Figure 1–15 An Asgard archaeon is caught clutching a pair of prokaryotic
partners. A scanning electron micrograph shows that an elaborate network of membranous
branches springs from the body of this cultured archaeal cell. These protrusions are wrapped
around two other prokaryotic species—one bacterial, one archaeal—that were isolated as
ectosymbionts along with the Asgard cell. This unusual archaeon was cultured for more
than 2000 days in a bioreactor that mimicked conditions on the seabed floor; during this
period, the Asgard cells divided once about every 20 days—compared to bacteria such as E.
coli, which divide once every 20 minutes. (From H. Imachi et al., Nature 577:519–525,
2020.)
At first biologists believed that archaea occupied only the most extreme environments on
Earth: the hot acid of volcanic springs, the airless depths of marine sediments, the sludge of
sewage treatment plants, the icy pools that lie beneath the frozen surface of Antarctica, or the
acidic, oxygen-free environment of a cow’s stomach, where they break down ingested cellulose

and generate methane gas. Many of these inhospitable environments resemble the harsh
conditions that must have existed on the primitive Earth, when living things first evolved. But we
now know that archaea live everywhere, even on our skin. Archaea are believed to be the
predominant form of life in soil and seawater, and they play a major role in recycling nitrogen
and carbon, two of the most important elements for the biology of all cells.
DNA sequencing revealed an additional surprise regarding archaeal biology: although
archaea resemble bacteria in their outward appearance, their genomes are much more closely
related to those of eukaryotes. The archaea with the most eukaryotic-like genes belong to a
lineage called Asgard (see Figure 1–10). These archaea were initially identified by sequencing
DNA fragments collected from Loki’s Castle, a hydrothermal vent in the seabed off the coast of
Greenland. While this sequence immediately revealed Asgard’s close kinship with eukaryotes,
the most stunning discovery would not come until scientists managed to grow Asgard cells in the
lab—a heroic feat that took 12 years of carefully tending to a custom-made bioreactor filled with
seafloor muck and bathed in methane gas. Examining these cultured archaea in an electron
microscope, the researchers were treated to a view of a cell that looks like no other living
prokaryote: a jumble of long, meandering branches extends from its small cell body. But even
more astonishing, the Asgard archaeon was observed to harbor a pair of ectosymbionts: one
bacterium and an unrelated archaeon that appear to be entangled in the strange creature’s spindly
embrace (Figure 1–15). The discovery of this unusual archaeon—with its prokaryotic associates
—suggests a mechanism by which an ancestral cell might have ultimately captured and
established a relationship with an aerobic bacterium: the step that initiated the evolution of the
eukaryotic lineage.
Glossary
eukaryote
An organism whose cells have a distinct nucleus and cytoplasm.
prokaryote
Major category of living cells distinguished by the absence of a nucleus; includes the
archaea and the eubacteria (commonly called bacteria).
bacterium
Microscopic organism that is a member of one of the two divisions of prokaryotes; some
species cause disease. The term is sometimes used to refer to any prokaryotic
microorganism, although the world of prokaryotes also includes archaea, which are only
distantly related. (See also archaeon.)
archaeon
Microscopic organism that is a member of one of the two divisions of prokaryotes; often
found in hostile environments such as hot springs or concentrated brine. (See also
bacterium.)

THE EUKARYOTIC CELL
Eukaryotic cells are typically 1000 to 10,000 times larger in volume than most bacteria and
archaea. Although some live independent lives as single-celled organisms, such as amoebae and
yeasts (Figure 1–16), others live in multicellular assemblies. As we have seen, all of the more
complex multicellular organisms—including plants, animals, and fungi such as mushrooms—are
formed from eukaryotic cells.
Figure 1–16 Yeasts are simple, free-living eukaryotes. The cells shown in this
micrograph belong to the species of yeast, Saccharomyces cerevisiae, used to make dough
rise and turn malted barley juice into beer. As can be seen in this image, the cells reproduce
by growing a bud and then dividing asymmetrically into a large mother cell and a small

daughter cell; for this reason, they are called budding yeast.
By definition, all eukaryotic cells have a nucleus. But possession of a nucleus goes hand-inhand
with possession of a variety of other organelles, most of which are membrane-enclosed and
common to all eukaryotic organisms but absent in prokaryotes. In this section, we take a look at
the main organelles found in eukaryotic cells from the point of view of their functions, and we
consider how they came to serve the roles they have in the life of the eukaryotic cell. Unraveling
the roles these organelles play in the life of a eukaryotic cell is one of the crowning achievements
of biological exploration, and it laid the foundation for understanding the biology of our own
cells—and how these systems become impaired by aging and disease.
The Nucleus Is the Information Store of the Cell
The nucleus is typically the most prominent organelle in a eukaryotic cell (Figure 1–17). It is
enclosed within two concentric membranes that form the nuclear envelope, and it contains
molecules of DNA—extremely long polymers that encode the genetic information of the
organism. In the light microscope, these giant DNA molecules become visible as individual
chromosomes when they become more compact before a cell divides into two daughter cells
(Figure 1–18). Bacteria and archaea also store their genetic information in the form of DNA;
however, these cells do not keep their DNA corralled inside a nuclear envelope, segregated from
the rest of the cell contents.
Figure 1–17 The nucleus contains most of the DNA in a eukaryotic cell. (A) This
drawing of a typical animal cell shows its extensive system of membrane-enclosed
organelles. The nucleus is colored brown, the nuclear envelope is green, and the cytoplasm

(the interior of the cell outside the nucleus) is white. (B) An electron micrograph of the
nucleus in a mammalian cell. Individual chromosomes are not visible because at this stage
of the cell-division cycle, the DNA molecules are dispersed as fine threads throughout the
nucleus. (B, by permission of E.L. Bearer and Daniel S. Friend.)
Figure 1–18 Chromosomes become visible when a cell is about to divide. As a
eukaryotic cell prepares to divide, its DNA molecules become progressively more
compacted (condensed), forming wormlike chromosomes that can be distinguished in the
light microscope (see also Figure 1–5). The photographs here show three successive steps in
this chromosome condensation process in a cultured cell from a newt’s lung; note that in the
last micrograph on the right, the nuclear envelope has broken down in preparation for the
chromosomes to move into position for cell division. (Courtesy of Conly L. Rieder, Albany,
New York.) (Dynamic Figure) In an early fly embryo (below), nuclei divide without
accompanying cell division, producing a cell that has thousands of nuclei. These nuclei
divide synchronously, their chromosomes (green) condensing and being pulled into
daughter nuclei by a cytoskeletal machine (red) called the mitotic spindle. (Courtesy of
William Sullivan.) For another view of the mitotic spindle, see Figure 1–29.
Mitochondria Generate Usable Energy from Food
Molecules
Mitochondria (singular, mitochondrion) are present in essentially all eukaryotic cells, and
they are among the most conspicuous organelles present in the cytoplasm (see Figure 1–8B).
When seen with an electron microscope, individual mitochondria are found to be enclosed in two
separate membranes, with the inner membrane formed into folds that project into the interior of
the organelle (Figure 1–19).

Figure 1–19 Mitochondria have a distinctive internal structure. (A) An electron
micrograph of a cross section of a mitochondrion reveals the extensive infolding of the
inner membrane. (B) This three-dimensional representation of the arrangement of the
mitochondrial membranes shows the smooth outer membrane (gray) and the highly
convoluted inner membrane (red). The inner membrane contains most of the proteins
responsible for energy production in eukaryotic cells; it is highly folded to provide a
large surface area for this activity. (C) In this schematic cell, the innermost
compartment of the mitochondrion is colored orange. (A, courtesy of Daniel S. Friend,
by permission of E.L. Bearer.)

Microscopic examination by itself, however, gives little indication of what mitochondria
actually do for the cell. Their function was discovered by breaking open cells and then spinning
the soup of cell fragments in a centrifuge; this treatment separates organelles and other
subcellular structures according to their size and density. Purified mitochondria were then tested
to see what chemical processes they could perform. This approach revealed that mitochondria are
generators of chemical energy for the cell. They harness the energy from the oxidation of food
molecules, such as sugars, to produce adenosine triphosphate, or ATP—the basic chemical fuel
that powers most of the cell’s activities. Because the mitochondrion consumes oxygen and
releases CO 2 in the course of this activity, the entire process is called cell respiration—
essentially, breathing at the level of the cell. Without mitochondria, eukaryotes such as animals,
fungi, and plants would be unable to use oxygen to extract the energy they need from the food
molecules that nourish them, a process we consider in detail in Chapter 14.
Mitochondria contain their own DNA and reproduce by dividing. Their strong resemblance
—both in appearance and in DNA sequence—to modern-day bacteria provides persuasive
evidence that mitochondria evolved from an aerobic bacterium that was engulfed by an anaerobic
ancestor of present-day eukaryotic cells. This event created a symbiotic relationship that provided
both partner cells with metabolic support, enabling them to survive and reproduce. The
observations of the Asgard archaeon in close association with its prokaryotic partner cells
strongly suggest that the original capturing cell was an archaeon (Figure 1–20).

Figure 1–20 Mitochondria are thought to have evolved from engulfed bacteria. It is
extremely likely that mitochondria evolved from aerobic bacteria that were captured and
subsequently engulfed by an ancient, anaerobic archaeal cell. According to this model, the
surface protrusions of an ancient, Asgard-like archaeon expanded and surrounded an aerobic
bacterium, fostering a symbiotic relationship between the two cells. Over time, the
expanded protrusions fused with one another, trapping the bacterium as an endosymbiont
within the body of the archaeon, where it initially remained enclosed by an internal
membrane derived from the archaeal plasma membrane. At some point, the symbiont
escaped from this archaeal membrane and entered the cell’s cytosol, where it eventually
evolved into a mitochondrion containing DNA and surrounding membranes derived from
the engulfed bacterium. As indicated, the archaeal plasma membrane that folded inward
during the process of protrusion, expansion, and fusion is proposed to have formed both the
nuclear envelope and the internal membrane-enclosed organelles, such as the endoplasmic
reticulum. (Adapted from H. Imachi et al., Nature 577:519–525, 2020 and from D.A. Baum
and B. Baum, BMC Biol. 12:76–92, 2014.)
Chloroplasts Capture Energy from Sunlight
Chloroplasts are large, green organelles that are found in the cells of plants and algae, but not
in the cells of animals or fungi. These organelles have an even more complex structure than
mitochondria: in addition to their two surrounding membranes, they possess internal stacks of
membranes containing the green pigment chlorophyll (Figure 1–21).

Figure 1–21 Chloroplasts in plant cells capture the energy of sunlight. (A) Seen in
this light micrograph, a single cell isolated from a leaf of a flowering plant has many green
chloroplasts. (B) A drawing of a single chloroplast, showing the inner and outer membranes,
as well as the highly folded system of internal membranes containing the green chlorophyll
molecules that absorb light energy. (A, courtesy of Preeti Dahiya.)
Chloroplasts carry out photosynthesis—trapping the energy of sunlight in their chlorophyll
molecules and using this energy to drive the manufacture of energy-rich sugar molecules. In the
process, they release oxygen as a molecular by-product. Plant cells can later extract this stored
chemical energy when they need it, just as animal cells do: by oxidizing these sugars and their
breakdown products, mainly in the mitochondria. Chloroplasts thus enable plants to get their
energy directly from sunlight. They also allow plants to produce the food molecules—and the
oxygen—that mitochondria use to generate chemical energy in the form of ATP. How these
organelles work together is discussed in Chapter 14.
Like mitochondria, chloroplasts contain their own DNA, reproduce by dividing in two, and
are thought to have evolved from bacteria—in this case, from photosynthetic bacteria that were
engulfed by eukaryotic-like cells that had already acquired mitochondria (Figure 1–22).

Figure 1–22 Eukaryotes contain a combination of genomes that originally derived
from archaea and bacteria. The bacterial and archaean lineages diverged from one another
very early in the evolution of life on Earth. Some time later, archaeal cells are thought to
have acquired mitochondria by establishing symbiotic relationships with aerobic bacteria;
later still, a subset of these single-celled eukaryotes acquired chloroplasts. Mitochondria are
essentially the same in plants, animals, and fungi, and therefore were presumably acquired
before these lines diverged about 1.5 billion years ago.
Internal Membranes Create Intracellular Compartments
with Different Functions
Nuclei, mitochondria, and chloroplasts are not the only membrane-enclosed organelles inside
eukaryotic cells. The cytoplasm contains a profusion of other organelles that are surrounded by
single membranes (see Figure 1–8A). Most of these structures are involved with the cell’s ability
to import raw materials and to export both useful substances and waste products that are
produced by the cell (a topic we discuss in detail in Chapter 12).
The endoplasmic reticulum (ER) is an irregular maze of interconnected spaces enclosed by a
membrane (Figure 1–23). It is the site where most cell-membrane components, as well as
materials destined for export from the cell, are made. This organelle is especially extensive in
cells that are specialized to secrete large amounts of protein. Stacks of flattened, membraneenclosed
sacs constitute the Golgi apparatus (Figure 1–24), which modifies and packages
molecules made in the ER that are destined to be either secreted from the cell or transported to
another cell compartment. Lysosomes are small, irregularly shaped organelles in which
intracellular digestion occurs, releasing nutrients from ingested food particles into the cytosol
and breaking down unwanted molecules for either recycling within the cell or excretion from the

cell. Indeed, many of the large and small molecules within the cell are constantly being broken
down and remade. Peroxisomes are small, membrane-enclosed vesicles that provide a
sequestered environment for a variety of reactions in which hydrogen peroxide is used to
inactivate toxic molecules. Membranes also form many types of small transport vesicles that
ferry materials between one membrane-enclosed organelle and another. All of these membraneenclosed
organelles are highlighted in Figure 1–25A.
Figure 1–23 The endoplasmic reticulum produces many of the components of a
eukaryotic cell. (A) Schematic diagram of an animal cell shows the endoplasmic reticulum
(ER) in green. (B) Electron micrograph of a thin section of a mammalian pancreatic cell,
which is specialized for protein secretion, shows a small part of the ER, which is vast in this
cell type. Note that the ER is continuous with the membranes of the nuclear envelope. The
black particles studding the region of the ER (and nuclear envelope) shown here are
ribosomes, structures that translate RNAs into proteins. Because of its appearance,
ribosome-coated ER is often called “rough ER” to distinguish it from the “smooth ER,”
which does not have ribosomes bound to it. (B, courtesy of Lelio Orci.)

Figure 1–24 The Golgi apparatus is composed of a stack of flattened, membraneenclosed
discs. (A) Schematic diagram of an animal cell with the Golgi apparatus colored
red. (B) More realistic drawing of the Golgi apparatus. Some of the vesicles seen nearby
have pinched off from the Golgi stack; others are destined to fuse with it. Only one stack is
shown here, but several can be present in a cell. (C) Electron micrograph that shows the
Golgi apparatus in a typical animal cell. (C, courtesy of Brij J. Gupta.)

Figure 1–25 Membrane-enclosed organelles are distributed throughout the
eukaryotic cell cytoplasm. (A) The various types of membrane-enclosed organelles, shown
in different colors, are each specialized to perform a different function. (B) The part of the
cytoplasm that fills the space outside of these organelles is called the cytosol (colored blue).

Figure 1–26 Eukaryotic cells engage in continual endocytosis and exocytosis across
their plasma membrane. They import extracellular materials by endocytosis and secrete
intracellular materials by exocytosis. Endocytosed material is first delivered to membraneenclosed
organelles called endosomes (discussed in Chapter 15).
A continual exchange of materials takes place between the endoplasmic reticulum, the Golgi
apparatus, the lysosomes, the plasma membrane, and the outside of the cell. The exchange is
mediated by transport vesicles that pinch off from the membrane of one organelle and fuse with
another, like tiny soap bubbles that bud from and combine with other bubbles. At the surface of
the cell, for example, portions of the plasma membrane tuck inward and pinch off to form
vesicles that carry material captured from the external medium into the cell—a process called
endocytosis (Figure 1–26). Animal cells can engulf very large particles, or even entire foreign

cells, by endocytosis. In the reverse process, called exocytosis, vesicles from inside the cell fuse
with the plasma membrane and release their contents into the external medium (see Figure 1–
26); most of the hormones and signal molecules that allow cells to communicate with one
another are secreted from cells by exocytosis. How membrane-enclosed organelles move
proteins and other molecules from place to place inside the eukaryotic cell is discussed in detail
in Chapter 15.
The Cytosol Is a Concentrated Aqueous Gel of Large
and Small Molecules
If we were to strip the plasma membrane from a eukaryotic cell and remove all of its
membrane-enclosed organelles—including the nucleus, endoplasmic reticulum, Golgi apparatus,
mitochondria, chloroplasts, and so on—we would be left with the cytosol (Figure 1–25B). In
other words, the cytosol is the part of the cytoplasm that is not contained within intracellular
membranes. In most cells, the cytosol is the largest single compartment. It contains a host of
large and small molecules, crowded together so closely that it behaves more like a water-based
gel than a liquid solution (Figure 1–27). The cytosol is the site of many of the chemical reactions
that are fundamental to the cell’s existence. The early steps in the breakdown of nutrient
molecules take place in the cytosol, for example, and it is here that most proteins are made by
ribosomes.

Figure 1–27 The cytosol is extremely crowded. This atomically detailed model of the
cytosol of E. coli is based on the sizes and concentrations of 50 of the most abundant large
molecules present in the bacterium. RNAs, proteins, and ribosomes are shown in different
colors (Movie 1.2). (From S.R. McGuffee and A.H. Elcock, PLoS Comput. Biol.
6:e1000694, 2010.)
The Cytoskeleton Is Responsible for Directed Cell
Movements
The cytosol is not merely a thin, structureless soup of chemicals and organelles. Using an
electron microscope, one can see that in eukaryotic cells the cytosol is crisscrossed by long, fine
filaments. Frequently, the filaments are seen to be anchored at one end to the plasma membrane

or to radiate out from a central site adjacent to the nucleus. This system of protein filaments,
called the cytoskeleton, is composed of three major filament types (Figure 1–28). The thinnest
of these filaments are the actin filaments; they are abundant in all eukaryotic cells but occur in
especially large numbers inside muscle cells, where they serve as a central part of the machinery
responsible for muscle contraction. The thickest filaments in the cytosol are called microtubules
(see Figure 1–7B), because they have the form of minute hollow tubes; in dividing cells, they
become reorganized into a spectacular array that helps pull the duplicated chromosomes apart
and distribute them equally to the two daughter cells (Figure 1–29). Intermediate in thickness
between actin filaments and microtubules are the intermediate filaments, which serve to
strengthen most animal cells. These three types of filaments, together with other proteins that
attach to them, form a system of girders, ropes, and motors that gives the cell its mechanical
strength, controls its shape, and drives and guides its movements (Movie 1.3 and Movie 1.4).
Figure 1–28 The cytoskeleton is a network of protein filaments that can be seen
crisscrossing the cytoplasm of eukaryotic cells. The three major types of filaments can be
detected using different fluorescent stains. Shown here are (A) actin filaments, (B)
microtubules, and (C) intermediate filaments. (A, Molecular Expressions at Florida State
University; B, courtesy of Nancy Kedersha; C, courtesy of Clive Lloyd.)

Figure 1–29 Microtubules help segregate the chromosomes in a dividing animal
cell. A transmission electron micrograph and schematic drawing show duplicated
chromosomes attached to the microtubules of a mitotic spindle (discussed in Chapter 18).
When a cell divides, its nuclear envelope breaks down (see Figure 1–18) and its DNA
condenses into visible chromosomes, each of which has duplicated to form a pair of
conjoined chromosomes that will ultimately be pulled apart into separate daughter cells by
the spindle microtubules. See also Panel 1–1, pp. 12–13. (Photomicrograph courtesy of
Conly L. Rieder, Albany, New York.)
QUESTION 1–5
Suggest a reason why it might have been advantageous for eukaryotic cells to have evolved
elaborate internal membrane systems that allow them to import substances from the outside, as
shown in Figure 1–26.
Because the cytoskeleton governs the internal organization of the cell as well as its external
features, it is as necessary to a plant cell—which is boxed in by a tough cell wall—as it is to an
animal cell that freely bends, stretches, swims, or crawls. In a plant cell, for example, organelles
such as mitochondria are driven in a constant stream around the cell interior along cytoskeletal
tracks (Movie 1.5). And animal cells and plant cells alike depend on the cytoskeleton to separate
their internal components into two daughter cells during cell division (see Figure 1–29).
The cytoskeleton’s role in cell division may be its most ancient function. Even bacteria
contain proteins that are distantly related to those that form the cytoskeletal elements involved in
eukaryotic cell division, showing that this class of proteins was present in the very earliest cells;
in bacteria, these proteins also form filaments that play a part in cell division. We examine the
cytoskeleton in detail in Chapter 17, discuss its role in cell division in Chapter 18, and review
how it responds to signals from outside the cell in Chapter 16.

The Cytosol Is Far from Static
The cell interior is in constant motion. The cytoskeleton is a dynamic jungle of protein ropes
that are continually being strung together and taken apart; its filaments can assemble and then
disappear in a matter of minutes. Motor proteins use the energy stored in molecules of ATP to
trundle along these tracks and cables, carrying organelles and proteins throughout the cytoplasm,
and racing across the width of the cell in seconds. In addition, the large and small molecules that
fill every free space in the cell are knocked to and fro by random thermal motion, constantly
colliding with one another and with other structures in the cell’s crowded cytosol.
Of course, neither the bustling nature of the cell’s interior nor the details of cell structure
were appreciated when scientists first peered at cells in a microscope; our knowledge of cell
structure accumulated slowly.
A few of the key discoveries are listed in Table 1–1. In addition, Panel 1–2 (p. 27)
summarizes the main differences between animal, plant, and bacterial cells.
TABLE 1–1 HISTORICAL LANDMARKS IN DETERMINING CELL
STRUCTURE
1665
1674
1833
1839
Hooke uses a primitive microscope to describe small chambers in sections
of cork that he calls “cells”
van Leeuwenhoek reports his discovery of protozoa. Nine years later, he
sees bacteria for the first time
Brown publishes his microscopic observations of orchids, clearly
describing the cell nucleus
Schleiden and Schwann propose the cell theory, stating that the nucleated
cell is the universal building block of plant and animal tissues
1857 von Kölliker describes mitochondria in muscle cells
1879
1881
1898
1902
1952
1957
Flemming describes with great clarity chromosome behavior during
mitosis in animal cells
Ramón y Cajal and other histologists develop staining methods that reveal
the structure of nerve cells and the organization of neural tissue
Golgi first sees and describes the Golgi apparatus by staining cells with
silver nitrate
Boveri links chromosomes and heredity by observing chromosome
behavior during sexual reproduction
Palade, Porter, and Sjöstrand develop methods of electron microscopy that
enable many intracellular structures to be seen for the first time. In one of the
first applications of these techniques, Huxley shows that muscle contains
arrays of protein filaments—the first evidence of a cytoskeleton
Robertson describes the bilayer structure of the cell membrane, seen for
the first time in the electron microscope
Kendrew describes the first detailed protein structure (sperm whale

1960 myoglobin) to a resolution of 0.2 nm, using x-ray crystallography. Perutz
proposes a lower-resolution structure for hemoglobin
1965
de Duve and colleagues use a cell-fractionation technique to separate
peroxisomes, mitochondria, and lysosomes from a preparation of rat liver
1968 Petráˇn and collaborators make the first confocal microscope
1970
Frye and Edidin use fluorescent antibodies to show that plasma membrane
molecules can diffuse in the plane of the membrane, indicating that cell
membranes are fluid
1974 Lazarides and Weber use fluorescent antibodies to stain the cytoskeleton
1994
Chalfie and collaborators introduce green fluorescent protein (GFP) as a
marker to follow the behavior of proteins in living cells
1990s–
2000s
Betzig, Hell, and Moerner develop techniques for superresolution
fluorescence microscopy that allow observation of biological molecules too
small to be resolved by conventional light or fluorescence microscopy
PANEL 1–2 CELL ARCHITECTURE